Preparation having antioxidant properties

ABSTRACT

The invention relates to a preparation having antioxidant properties, comprising at least one compound of the formula I  
                 
 
     where R 1  to R 10  may be identical or different and are selected from H, OR 11 , straight-chain or branched C 1 - to C 20 -alkyl groups, straight-chain or branched C 3 - to C 20 -alkenyl groups, straight-chain or branched C 1 - to C 20 -hydroxyalkyl groups, where the hydroxyl group may be bonded to a primary or secondary carbon atom of the chain and furthermore the alkyl chain may also be interrupted by oxygen, and/or C 3 - to C 10 -cycloalkyl groups and/or C 3 - to C 12 -cycloalkenyl groups, where the rings may each also be bridged by —(CH 2 ) n — groups, where n=1 to 3, where all OR 11  are, independently of one another, OH, C 1 - to C 20 -alkoxy groups, C 3 - to C 20 -alkenyloxy groups, straight-chain or branched C 1 - to C 20 -hydroxyalkoxy groups and/or C 3 - to C 10 -cycloalkoxy groups and/or C 3 - to C 12 -cycloalkenyloxy groups, where the rings may each also be bridged by —(CH 2 ) n — groups, where n=1 to 3, and/or mono- and/or oligoglycosyl radicals, with the proviso that at least 3 radicals from R 1  to R 7  are OH and that at least 2 pairs of adjacent —OH groups are present in the molecule, or R 2 , R 5  and R 6  are OH and the radicals R 1 , R 3 , R 4  and R 7-10  are H.

[0001] The present invention relates to a preparation having antioxidantproperties, and to the preparation and use thereof.

[0002] An example of an area of application of the preparationsaccording to the invention is cosmetics. The object of care cosmetics iswherever possible to obtain the impression of youthful skin. Inprinciple, there are various ways of achieving this object. For example,existing skin damage, such as irregular pigmentation or the developmentof wrinkles, can be compensated for by covering powders or creams.Another approach is to protect the skin against environmental influenceswhich lead to permanent damage and thus ageing of the skin. The idea istherefore to intervene in a preventative manner and thus to delay theageing process. One example of this is the UV filters already mentioned,which, as a result of absorption of certain wavelength ranges, preventor at least reduce skin damage. Whereas in the case of UV filters thedamaging event, the UV radiation, is screened off by the skin, anotherroute involves attempting to support the skin's natural defense orrepair mechanisms against the damaging event. Finally, a furtherapproach involves compensating for the weakening defense functions ofthe skin against harmful influences with increasing age by externallysupplying substances which are able to replace this diminishing defenseor repair function. For example, the skin has the ability to scavengefree radicals formed by external or internal stress factors. Thisability diminishes with increasing age, causing the ageing process toaccelerate with increasing age.

[0003] A certain degree of tanning of the skin is regarded in modernsociety as attractive and as an expression of vigor and sportiness. Inaddition to this desired action of the sun on the skin, a number ofundesired side effects occur, such as sunburn or premature skin ageingand wrinkling. Of particular importance here is the wavelength rangefrom 280 to 400 nm. This range covers UV-B rays having a wavelength ofbetween 280 and 320 nm, which play a crucial role in the formation ofsolar erythema, and also UV-A rays having a wavelength of between 320and 400 nm, which tan the skin, but also allow ageing, favor thetriggering of an erythematous reaction or can exacerbate this reactionin certain people or even trigger phototoxic or photoallergic andirritative reactions.

[0004] Skin damage is not caused just by sunlight, but also by otherexternal influences, such as cold or heat. Furthermore, the skinundergoes natural ageing, with the formation of wrinkles and a reductionin the elasticity of the skin.

[0005] A further difficulty in the preparation of cosmetics is thatactive ingredients which are intended to be incorporated into cosmeticpreparations are frequently unstable and can be damaged in thepreparation. The damage may be caused, for example, by a reaction withatmospheric oxygen or by absorption of UV rays. The molecules damaged inthis way may, for example, change their color and/or lose their activitythrough their structural change.

[0006] A known way of dealing with the problems described consists inadding antioxidants to the preparations.

[0007] According to CD Römpp Chemie Lexikon [CD Römpp Lexicon ofChemistry]—Version 1.0, Stuttgart/New York: Georg Thieme Verlag 1995,antioxidants are compounds which inhibit or prevent undesired changes inthe substances to be protected caused by the action of oxygen, interalia oxidative processes. Areas of application are, for example, inplastics and rubber for protection against ageing; in fats forprotection against rancidity, in oils, cattle feeds, automotive gasolineand jet fuels for protection against gumming, in transformer and turbineoil against sludge formation, and in flavors against odor impairment.Compounds that are effective as antioxidants are, inter alia, phenols,hydroquinones, pyrocatechols and aromatic amines which are substitutedby sterically hindering groups, and metal complexes thereof. Accordingto Römpp, the action of the antioxidants usually consists in that theyact as free-radical scavengers for the free radicals which arise duringautoxidation.

[0008] However, there continues to be a demand for skin-toleratedantioxidants which are also suitable for use in skin-care preparations.

[0009] An object of this invention is to provide a composition which hasa protective action against UV rays and/or exerts a protective actionagainst oxidative stress on body cells and/or counters skin ageing.

[0010] Upon further study of the specification and appended claims,further objects and advantages of this invention will become apparent tothose skilled in the art.

[0011] Surprisingly, it has been found that certain flavonoids areeminently suitable as antioxidants. A first subject-matter of thepresent invention is therefore a preparation having antioxidantproperties comprising at least one compound of the formula I

[0012] where R¹ to R¹⁰ may be identical or different and are selectedfrom

[0013] H

[0014] OR¹¹

[0015] straight-chain or branched C₁- to C₂₀-alkyl groups,

[0016] straight-chain or branched C₃- to C₂₀-alkenyl groups,

[0017] straight-chain or branched C₁- to C₂₀-hydroxyalkyl groups, wherethe hydroxyl group may be bonded to a primary or secondary carbon atomof the chain and furthermore the alkyl chain may also be interrupted byoxygen, and/or

[0018] C₃- to C₁₀-cycloalkyl groups and/or C₃- to C₁₂-cycloalkenylgroups, where the rings may each also be bridged by —(CH₂)_(n)— groups,where n=1 to 3,

[0019] where all OR¹¹ are, independently of one another,

[0020] OH

[0021] straight-chain or branched C₁- to C₂₀-alkoxy groups,

[0022] straight-chain or branched C₃- to C₂₀-alkenyloxy groups,

[0023] straight-chain or branched C₁- to C₂₀-hydroxyalkoxy groups, wherethe hydroxyl group(s) may be bonded to a primary or secondary carbonatom of the chain and furthermore the alkyl chain may also beinterrupted by oxygen, and/or

[0024] C₃- to C₁₀-cycloalkoxy groups and/or C₃- to C₁₂-cycloalkenyloxygroups, where the rings may each also be bridged by —(CH₂)_(n)— groups,where n=1 to 3, and/or

[0025] mono- and/or oligoglycosyl radicals,

[0026] with the proviso that:

[0027] at least 3 radicals from R¹ to R⁷ are OH and that at least 2pairs of adjacent —OH groups are present in the molecule (“adjacent”meaning that the OH groups are on carbon atoms adjacent in the ring),

[0028] or R², R⁵ and R⁶ are OH and the radicals R¹, R³, R⁴ and R⁷⁻¹⁰ areH.

[0029] Of the phenols having an antioxidative action, the polyphenols,some of which are naturally occurring, are of particular interest forapplications in the pharmaceutical, cosmetic or nutrition sector. Forexample, the flavonoids or bioflavonoids, which are principally known asplant dyes, frequently have an antioxidant potential. K. Lemanska, H.Szymusiak, B. Tyrakowska, R. Zielinski, I. M. C. M. Rietjens; CurrentTopics in Biophysics 2000, 24(2), 101-108, are concerned with effects ofthe substitution pattern of mono- and dihydroxyflavones. It is observedtherein that dihydroxyflavones containing an OH group adjacent to theketo function or OH groups in the 3′,4′- or 6,7- or 7,8-position haveantioxidative properties, while other mono- and dihydroxyflavones insome cases do not have antioxidative properties.

[0030] Quercetin (cyanidanol, cyanidenolon 1522, meletin, sophoretin,ericin, 3,3′,4′,5,7-pentahydroxyflavone) is frequently mentioned as aparticularly effective antioxidant (for example C. A. Rice-Evans, N. J.Miller, G. Paganga, Trends in Plant Science 1997, 2(4), 152-159). K.Lemanska, H. Szymusiak, B. Tyrakowska, R. Zielinski, A. E. M. F.Soffers, I. M. C. M. Rietjens; Free Radical Biology & Medicine 2001,31(7), 869-881, have investigated the pH dependence of the antioxidantaction of hydroxyflavones. Quercetin exhibits the greatest activityamongst the structures investigated over the entire pH range.

[0031] DE 197 55 504 A1 describes the use of flavones and flavonoidsagainst UV-induced decomposition of dibenzoylnethane and itsderivatives.

[0032] WO 02/00214 describes the use of certain flavone derivatives forthe preparation of oral medicaments for the systemic treatment andprophylaxis of WV-induced dermatosis, in particular of polymorphic lightdermatosis and its sub-forms, and/or undesired long-term consequences ofWV irradiation, particularly light ageing. Preferred flavone derivativeshere are, in particular, naturally occurring bioflavonoids, such asrutin, naringin, naringenin, hesperidin, hesperetin, taxifolin, etc.,and derivatives thereof, such as troxerutin and monoxerutin.

[0033] International Patent Application WO 00/61095 describes mixturesof polyphenols with vitamins. These mixtures are suitable for use incosmetic or dermatological compositions and are optimized for scavengingfree radicals, such as hydroxyl free radicals or peroxides. Particularpreference is given here to the combination of troxerutin withα-tocopherol succinate and ascorbyl palmitate.

[0034] The advantages of the compositions according to the inventionhere are, in particular, the antioxidant action and the good skintolerability. In addition, the compounds described here are preferablycolorless or have only a weak color and thus only result in slightdiscoloration of the preparations, or none at all. Of particularadvantage is the particular action profile of the compounds to beemployed in accordance with the invention, which is evident in the DPPHassay (see below) in a high capacity for scavenging free radicals(EC₅₀), a time-delayed action (T_(EC50)>120 min) and thus a moderate tohigh anti-free-radical efficiency (AE). In addition, the compounds ofthe formula I combine antioxidative properties with UV absorption in theUV-A and/or UV-B region in the molecule.

[0035] The present invention therefore also relates to the use of thecompounds of the formula I, as indicated above, as antioxidants having along-lasting action or for the preparation of a composition havingantioxidant properties.

[0036] The compositions here are usually either compositions which canbe applied topically, for example cosmetic or dermatologicalformulations, or foods or food supplements. In this case, thecompositions comprise a cosmetically or dermatologically orfood-suitable excipient and, depending on the desired property profile,optionally further suitable ingredients.

[0037] The compounds of the formula I are, in accordance with theinvention, typically employed in the compositions in amounts of from0.01 to 20% by weight, more preferably in amounts of from 0.1% by weightto 10% by weight and particularly preferably in amounts of from 1 to 8%by weight. The person skilled in the art is presented with absolutely nodifficulties in selecting the amounts appropriately depending on theintended action of the composition.

[0038] Preference is therefore also given to compositions comprising atleast one compound of the formula I which is characterized in that atleast two adjacent radicals of the radicals R¹ to R⁴ are OH and at leasttwo adjacent radicals of the radicals R⁵ to R⁷ are OH.

[0039] Particularly preferred compositions comprise at least onecompound of the formula I which is characterized in that at least threeadjacent radicals of the radicals R¹ to R⁴ are OH, preferably with theradicals R¹ to R³ being OH.

[0040] In order that the compounds of the formula I are able to developtheir positive action as free-radical scavengers on the skinparticularly well, it may be preferred to allow the compounds of theformula I to penetrate into deeper skin layers. Several possibilitiesare available for this purpose. Firstly, the compounds of the formula Ican have an adequate lipophilicity in order to be able to penetratethrough the outer skin layer into epidermal layers. As a furtherpossibility, corresponding transport agents, for example liposomes,which enable transport of the compounds of the formula I through theouter skin layers may also be provided in the preparation. Finally,systemic transport of the compounds of the formula I is alsoconceivable. The composition is then designed, for example, in such away that it is suitable for oral administration.

[0041] In general, the substances of the formula I act as free-radicalscavengers. Free radicals of this type are not generated only bysunlight, but instead are formed under various conditions. Examples areanoxia, which blocks the flow of electrons upstream of the cytochromeoxidases and causes the formation of superoxide free-radical anions;inflammation associated, inter alia, with the formation of superoxideanions by the membrane NADPH oxidase of the leucocytes, but alsoassociated with the formation (through disproportionation in thepresence of iron(II) ions) of the hydroxyl free radicals and otherreactive species which are normally involved in the phenomenon ofphagocytosis; and lipid autooxidation, which is generally initiated by ahydroxyl free radical and produces lipidic alkoxy free radicals andhydroperoxides.

[0042] It is assumed that the preferred compounds of the formula I alsoact as enzyme inhibitors. They presumably inhibit histidinedecarboxylase, protein kinases, elastase, aldose reductase andhyaluronidase, and therefore enable the intactness of the basicsubstance of vascular sheaths to be maintained. Furthermore, theypresumably inhibit non-specifically catechol O-methyl transferase,causing the amount of available catecholamine and thus the vascularstrength to be increased. Furthermore, they inhibit AMPphosphodiesterase, giving the substances potential for inhibitingthrombocyte aggregation.

[0043] Owing to these properties, the compositions according to theinvention are, in general, suitable for immune protection and for theprotection of DNA and RNA. In particular, the compositions are suitablefor the protection of DNA and RNA against oxidative attack, against freeradicals and against damage due to radiation, in particular UVradiation. A further advantage of the compositions according to theinvention is cell protection, in particular protection of Langerhanscells against damage due to the above-mentioned influences. All theseuses and the use of the compounds of the formula I for the preparationof compositions which can be employed correspondingly are expressly alsoa subject-matter of the present invention.

[0044] In particular, preferred compositions according to the inventionare also suitable for the treatment of skin diseases associated with adefect in keratinisation which affects differentiation and cellproliferation, in particular for the treatment of acne vulgaris, acnecomedonica, polymorphic acne, acne rosaceae, nodular acne, acneconglobata, age-induced acne, acne which arises as a side effect, suchas acne solaris, medicament-induced acne or acne professionalis, for thetreatment of other defects in keratinisation, in particular ichthyosis,ichthyosiform states, Darier's disease, keratosis palmoplantaris,leucoplasia, leucoplasiform states, herpes of the skin and mucousmembrane (buccal) (lichen), for the treatment of other skin diseasesassociated with a defect in keratinisation and which have aninflammatory and/or immunoallergic component and in particular all formsof psoriasis which affect the skin, mucous membranes and fingers andtoenails, and psoriatic rheumatism and skin atopia, such as eczema orrespiratory atopia, or hypertrophy of the gums, it furthermore beingpossible for the compounds to be used for some inflammations which arenot associated with a defect in keratinisation, for the treatment of allbenign or malignant excrescence of the dermis or epidermis, which may beof viral origin, such as verruca vulgaris, verruca plana,epidermodysplasia verruciformis, oral papillomatosis, papillomatosisflorida, and excrescence which may be caused by UV radiation, inparticular epithelioma baso-cellulare and epithelioma spinocellulare,for the treatment of other skin diseases, such as dermatitis bullosa anddiseases affecting the collagen, for the treatment of certain eyediseases, in particular corneal diseases, for overcoming or combatinglight-induced skin ageing associated with ageing, for reducingpigmentation and keratosis actinica and for the treatment of alldiseases associated with normal ageing or light-induced ageing, for theprevention or healing of wounds/scars of atrophia of the epidermisand/or dermis caused by locally or systemically applied corticosteroidsand all other types of skin atrophia, for the prevention or treatment ofdefects in wound healing, for the prevention or elimination of stretchmarks caused by pregnancy or for the promotion of wound healing, forcombating defects in tallow production, such as hyperseborrhoea in acneor simple seborrhoea, for combating or preventing cancerlike states orpre-carcinogenic states, in particular promyelocytic leukaemia, for thetreatment of inflammatory diseases, such as arthritis, for the treatmentof all virus-induced diseases of the skin or other areas of the body,for the prevention or treatment of alopecia, for the treatment of skindiseases or diseases of other areas of the body with an immunologicalcomponent, for the treatment of cardiovascular diseases, such asarteriosclerosis or hypertension, and of non-insulin-dependent diabetes,and for the treatment of skin problems caused by UV radiation.

[0045] The antioxidant action of the compounds of the formula I can bedemonstrated, for example, by means of 2,2-diphenyl-1-picrylhydrazyl(DPPH) assay. 2,2-Diphenyl-1-picrylhydrazyl is a free radical which isstable in solution. The unpaired electron results in a strong absorptionband at 515 nm, and the solution has a dark violet color. In thepresence of a free-radical scavenger, the electron is paired, theabsorption disappears, and the decoloration proceeds stoichiometricallytaking into account the electrons taken up. The absorbance is measuredin a photometer. The anti-free-radical property of the substance to betested is determined by measuring the concentration at which 50% of the2,2-diphenyl-1-picrylhydrazyl employed has reacted with the free-radicalscavenger. This concentration is expressed as EC₅₀, a value which can beconsidered to be a property of the substance under the given measurementconditions. The substance investigated is compared with a standard (forexample tocopherol). The EC₅₀ value here is a measure of the capacity ofthe respective compound to scavenge free radicals. The lower the EC₅₀value, the higher the capacity to scavenge free radicals. For thepurposes of this invention, the expression “a large or high capacity forscavenging free radicals” is used if the EC₅₀ value is lower than thatof tocopherol.

[0046] A further important aspect for the action of the antioxidants isthe time in which this EC₅₀ value is reached. This time, measured inminutes, gives the T_(EC50) value, which allows a conclusion to be drawnon the rate at which these antioxidants scavenge free radicals. For thepurposes of these inventions, antioxidants which reach this value withinless than 60 minutes are regarded as fast, while those which only reachthe EC₅₀ value after more than 120 minutes are regarded as having atime-delayed action.

[0047] The anti-free-radical efficiency (AE) (described in C.Sanchez-Moreno, J. A. Larrauri and F. Saura-Calixto in J. Sci. FoodAgric. 1998, 76(2), 270-276) is given by the above-mentioned quantitiesin accordance with the following relationship:${AE} = \frac{1}{{EC}_{50}T_{EC50}}$

[0048] A low AE (×10⁻³) is in the range up to about 10, a moderate AE isin the range from 10 to 20 and a high AE has in accordance with theinvention values above 20.

[0049] It may be particularly preferred in accordance with the inventionto combine fast-acting antioxidants with those having a slow ortime-delayed action. Typical weight ratios of the fast-actingantioxidants to time-delayed antioxidants are preferably in the rangefrom 10:1 to 1:10, more preferably in the range from 10:1 to 1:1, andfor skin-protecting compositions particularly preferably in the rangefrom 5:1 to 2:1. In other compositions which are likewise preferred inaccordance with the invention, it may, however, be advantageous for thepurposes of action optimization for more time-delayed antioxidants thanfast-acting antioxidants to be present. Typical compositions thenexhibit weight ratios of the fast-acting antioxidants to time-delayedantioxidants preferably in the range from 1:1 to 1:10, more preferablyin the range from 1:2 to 1:8.

[0050] The protective action against oxidative stress or against theeffect of free radicals can thus be further improved if the compositionscomprise one or more further antioxidants. the person skilled in the artbeing presented with absolutely no difficulties in selecting suitablyfast-acting or time-delayed antioxidants.

[0051] In a preferred embodiment of the present invention, thecomposition is therefore a composition for the protection of body cellsagainst oxidative stress, in particular for reducing skin ageing,characterized in that it preferably comprises one or more furtherantioxidants besides the one or more compounds of the formula I.

[0052] There are many proven substances known from the literature whichcan be used as antioxidants, for example amino acids (for exampleglycine, histidine, tyrosine, tryptophan) and derivatives thereof,imidazoles (for example urocanic acid) and derivatives thereof,peptides, such as D,L-carnosine, D-carnosine, L-carnosine andderivatives thereof (for example anserine), carotinoids, carotenes (forexample α-carotene, β-carotene, lycopene) and derivatives thereof,chlorogenic acid and derivatives thereof, lipoic acid and derivativesthereof (for example dihydrolipoic acid), aurothioglucose,propylthiouracil and other thiols (for example thioredoxin, glutathione,cysteine, cystine, cystamine and the glycosyl, N-acetyl, methyl, ethyl,propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ-linoleyl,cholesteryl and glyceryl esters thereof) and salts thereof, dilaurylthiodipropionate, distearyl thiodipropionate, thiodipropionic acid andderivatives thereof (esters, ethers, peptides, lipids, nucleotides,nucleosides and salts), and sulfoximine compounds (for examplebuthionine sulfoximines, homocysteine sulfoximine, buthionine sulfones,penta-, hexa- and heptathionine sulfoximine) in very low tolerated doses(for example pmol to μmol/kg), and also (metal) chelating agents (forexample α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin),α-hydroxy acids (for example citric acid, lactic acid, malic acid),humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTAand derivatives thereof, unsaturated fatty acids and derivativesthereof, vitamin C and derivatives (for example ascorbyl palmitate,magnesium ascorbyl phosphate, ascorbyl acetate), tocopherols andderivatives (for example vitamin E acetate), vitamin A and derivatives(for example vitamin A palmitate), and coniferyl benzoate of benzoinresin, rutinic acid and derivatives thereof, α-glycosyl rutin, ferulicacid, furfurylideneglucitol, carnosine, butylhydroxytoluene,butylhydroxyanisole, nordihydroguaiaretic acid, trihydroxybutyrophenone,quercetin, uric acid and derivatives thereof, mannose and derivativesthereof, zinc and derivatives thereof (for example ZnO, ZnSO₄), seleniumand derivatives thereof (for example selenomethionine), stilbenes andderivatives thereof (for example stilbene oxide, trans-stilbene oxide).

[0053] Mixtures of antioxidants are likewise suitable for use in thecosmetic preparations according to the invention. Known and commercialmixtures are, for example, mixtures comprising, as active ingredients,lecithin, L-(+)-ascorbyl palmitate and citric acid (for example Oxynex®AP), natural tocopherols, L-(+)-ascorbyl palmitate, L-(+)-ascorbic acidand citric acid (for example Oxynex® K LIQUID), tocopherol extracts fromnatural sources, L-(+)-ascorbyl palmitate, L-(+)-ascorbic acid andcitric acid (for example Oxynex® L LIQUID), DL-α-tocopherol,L-(+)-ascorbyl palmitate, citric acid and lecithin (for example Oxynex®LM) or butylhydroxytoluene (BHT), L-(+)-ascorbyl palmitate and citricacid (for example Oxynex® 2004). Antioxidants of this type are usuallyemployed with compounds of the formula I in compositions of this type inratios in the range from 1000:1 to 1:1000, preferably in amounts of from100:1 to 1:100.

[0054] The compositions according to the invention may comprise vitaminsas further ingredients. The cosmetic compositions according to theinvention preferably comprise vitamins and vitamin derivatives selectedfrom vitamin A, vitamin A propionate, vitamin A palmitate, vitamin Aacetate, retinol, vitamin B, thiamine chloride hydrochloride (vitaminB₁), riboflavin (vitamin B₂), nicotinamide, vitamin C (ascorbic acid),vitamin D, ergocalciferol (vitamin D₂), vitamin E, DL-α-tocopherol,tocopherol E acetate, tocopherol hydrogensuccinate, vitamin K₁, esculin(vitamin P active ingredient), thiamine (vitamin B₁), nicotinic acid(niacin), pyridoxine, pyridoxal, pyridoxamine, (vitamin B₆), pantothenicacid, biotin, folic acid and cobalamine (vitamin B₁₂), particularlypreferably vitamin A palmitate, vitamin C and derivatives thereof,DL-α-tocopherol, tocopherol E acetate, nicotinic acid, pantothenic acidand biotin. Vitamins are usually employed here with compounds of theformula I in ratios preferably in the range from 1000:1 to 1:1000, morepreferably in amounts of from 100:1 to 1:100.

[0055] The compounds of the formula I to be employed in accordance withthe invention generally also have a UV absorption in the UV-A and/orUV-B region. The flavonoids of the formula I to be employed inaccordance with the invention include broad-band UV filters, which canbe employed alone or in combination with further UV filters. Other,likewise preferred compounds of the formula I exhibit an absorptionmaximum in the transition region between UV-B and UV-A radiation. AsUV-A-II filters, they therefore advantageously supplement the absorptionspectrum of commercially available UV-B and UV-A-I filters.

[0056] In addition, preferred compounds of this type have advantages onincorporation into the compositions:

[0057] mono- and/or oligoglycosyl radicals improve the water solubilityof the compounds to be employed in accordance with the invention;

[0058] straight-chain or branched C₁- to C₂₀-alkoxy groups, inparticular long-chain alkoxy functions, such as ethylhexyloxy groups,increase the oil solubility of the compounds; i.e. the hydrophilicity orlipophilicity of the compounds according to the invention can becontrolled via a suitable choice of substituents.

[0059] Preferred mono- or oligosaccharide radicals are hexosyl radicals,in particular ramnosyl radicals and glucosyl radicals. However, otherhexosyl radicals, for example allosyl, altrosyl, galactosyl, gulosyl,idosyl, mannosyl and talosyl, may also advantageously be used. It mayalso be advantageous to use pentosyl radicals. The glycosyl radicals maybe linked to the basic structure by means of an α- or β-glycosidic link.A preferred disaccharide is, for example,6-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranoside.

[0060] However, in likewise preferred embodiments of the invention, thecompositions according to the invention may also contain compounds ofthe formula I which are insoluble or have low solubility in thecomposition matrix. In this case, the compounds are preferably dispersedin the cosmetic composition in finely divided form.

[0061] Compositions which are particularly preferred in accordance withthe invention also comprise pure UV filters in addition to the compoundsof the formula I.

[0062] On use of the dibenzoylmethane derivatives which are particularlypreferred as UV-A filters in combination with the compounds of theformula I, an additional advantage arises: the UV-sensitivedibenzoylnethane derivatives are additionally stabilized by the presenceof the compounds of the formula I. The present invention thereforefurthermore relates to the use of the compounds of the formula I for thestabilization of dibenzoylmethane derivatives in preparations.

[0063] In principle, all UV filters are suitable for combination withthe compounds of the formula I according to the invention. Particularpreference is given to UV filters whose physiological acceptability hasalready been demonstrated. Both for UVA and UVB filters, there are manyproven substances which are known from the literature, for examplebenzylidenecamphor derivatives, such as3-(4′-methylbenzylidene)-dl-camphor (for example Eusolex® 6300),3-benzylidenecamphor (for example Mexoryl® SD), polymers of N-{(2 and4)-[(2-oxobom-3-ylidene)methyl]benzyl} acrylamide (for example Mexoryl®SW), N,N,N-trimethyl-4-(2-oxobom-3-ylidenemethyl)anilinium methylsulfate(for example Mexoryl® SK) or (2-oxoborn-3-ylidene)toluene-4-sulfonicacid (for example Mexoryl® SL),

[0064] benzoyl- or dibenzoylmethanes, such as1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione (for exampleEusolex® 9020) or 4-isopropyldibenzoylmethane (for example Eusolex®8020),

[0065] benzophenones, such as 2-hydroxy-4-methoxybenzophenone (forexample Eusolex® 4360) or 2-hydroxy-4-methoxybenzophenone-5-sulfonicacid and its sodium salt (for example Uvinul® MS-40),

[0066] methoxycinnamic acid esters, such as octyl methoxycinnamate (forexample Eusolex® 2292), isopentyl 4-methoxycinnamate, for example as amixture of the isomers (for example Neo Heliopan® E 1000),

[0067] salicylate derivatives, such as 2-ethylhexyl salicylate (forexample Eusolex® OS), 4-isopropylbenzyl salicylate (for exampleMegasol®) or 3,3,5-trimethylcyclohexyl salicylate (for example Eusolex®HMS),

[0068] 4-aminobenzoic acid and derivatives, such as 4-aminobenzoic acid,2-ethylhexyl 4-(dimethylamino)benzoate (for example Eusolex® 6007) orethoxylated ethyl 4-aminobenzoate (for example Uvinul® P25),

[0069] phenylbenzimidazolesulfonic acids, such as2-phenylbenzimidazole-5-sulfonic acid and potassium, sodium andtriethanolamine salts thereof (for example Eusolex® 232),2,2-(1,4-phenylene)bisbenzimidazole-4,6-disulfonic acid and saltsthereof (for example Neoheliopan® AP) or2,2-(1,4-phenylene)bisbenzimidazole-6-sulfonic acid;

[0070] and further substances, such as

[0071] 2-ethylhexyl 2-cyano-3,3-diphenylacrylate (for example Eusolex®OCR),

[0072]3,3′-(1,4-phenylenedimethylene)bis(7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-ylmethanesulfonicacid and salts thereof (for example Mexoryl® SX),

[0073] 2,4,6-trianilino-(p-carbo-2′-ethylhexyl-1′-oxy)-1,3,5-triazine(for example Uvinul® T 150) and

[0074] hexyl 2-(4-diethylamino-2-hydroxybenzoyl)benzoate (for exampleUvinul® UVA Plus, BASF).

[0075] The compounds mentioned in the list should only be regarded asexamples. It is of course also possible to use other UV filters.

[0076] These organic UV filters are generally incorporated into cosmeticformulations preferably in an amount of from 0.5 to 10 percent byweight, more preferably 1-8%.

[0077] Further suitable organic UV filters are, for example,

[0078]2-(2H-benzotriazol-2-yl)-4-methyl-6-(2-methyl-3-(1,3,3,3-tetramethyl-1-(trimethylsilyloxy)disiloxanyl)propyl)phenol(for example Silatrizole®),

[0079] 2-ethylhexyl4,4′-[(6-[4-((1,1-dimethylethyl)aminocarbonyl)phenylamino]-1,3,5-triazine-2,4-diyl)diimino]bis(benzoate)(for example Uvasorb® HEB),

[0080] α-(trimethylsilyl)-ω-[trimethylsilyl)oxy]poly[oxy(dimethyl [andabout 6% ofmethyl[2-[p-[2,2-bis(ethoxycarbonyl]vinyl]phenoxy]-1-methyleneethyl] andapproximately 1.5% ofmethyl[3-[p-[2,2-bis(ethoxycarbonyl)vinyl]phenoxy]propenyl] and from 0.1to 0.4% of (methylhydrogen]silylene]] (n≈60) (CAS No. 207 574-74-1)

[0081]2,2′-methylenebis(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol)(CAS No. 103 597-45-1)

[0082] 2,2′-(1,4-phenylene)bis(1H-benzimidazole-4,6-disulfonic acid,monosodium salt) (CAS No. 180 898-37-7) and

[0083] 2,4-bis{[4-(2-ethylhexyloxy)-2-hydroxy]phenyl}-6-(4-methoxyphenyl)-1,3,5-triazine(CAS No. 103 597-45-, 187 393-00-6).

[0084] Further suitable UV filters are methoxyflavones corresponding tothe earlier German patent application DE 10232595.2.

[0085] Organic UV filters are generally incorporated into cosmeticformulations preferably in an amount of from 0.5 to 20 percent byweight, more preferably 1-15%.

[0086] Conceivable inorganic UV filters are those from the groupconsisting of titanium dioxides, such as, for example, coated titaniumdioxide (for example Eusolex® T-2000, Eusolex® T-AQUA), zinc oxides (forexample Sachtotec), iron oxides and also cerium oxides. These inorganicUV filters are generally incorporated into cosmetic compositionspreferably in an amount of from 0.5 to 20 percent by weight, morepreferably 2-10%.

[0087] Preferred compounds having UV-filtering properties are3-(4′-methylbenzylidene)-dl-camphor,1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione,4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octylmethoxycinnamate, 3,3,5-trimethylcyclohexyl salicylate, 2-ethylhexyl4-(dimethylamino)benzoate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate,2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium andtriethanolamine salts.

[0088] The protective action against the damaging effects of UVradiation can be optimized by combining one or more compounds of theformula I with further UV filters.

[0089] Optimized compositions may comprise, for example, the combinationof the organic UV filters 4′-methoxy-6-hydroxyflavone with1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione and3-(4′-methylbenzylidene)-dl-camphor. This combination gives rise tobroad-band protection, which can be supplemented by the addition ofinorganic UV filters, such as titanium dioxide microparticles.

[0090] All the said UV filters can also be employed in encapsulatedform. In particular, it is advantageous to employ organic UV filters inencapsulated form. In detail, the following advantages arise:

[0091] The hydrophilicity of the capsule wall can be set independentlyof the solubility of the UV filter. Thus, for example, it is alsopossible to incorporate hydrophobic UV filters into purely aqueouspreparations. In addition, the oily impression on application of thecomposition comprising hydrophobic UV filters, which is frequentlyregarded as unpleasant, is suppressed.

[0092] Certain UV filters, in particular dibenzoylmethane derivatives,exhibit only reduced photostability in cosmetic compositions.Encapsulation of these filters or compounds which impair thephotostability of these filters, such as, for example, cinnamic acidderivatives, enables the photostability of the entire composition to beincreased.

[0093] Skin penetration by organic UV filters and the associatedpotential for irritation on direct application to the human skin isrepeatedly being discussed in the literature. The encapsulation of thecorresponding substances which is proposed here suppresses this effect.

[0094] In general, encapsulation of individual UV filters or otheringredients enables preparation problems caused by the interaction ofindividual composition constituents with one another, such ascrystallization processes, precipitation and agglomerate formation, tobe avoided since the interaction is suppressed.

[0095] It is therefore preferred in accordance with the invention forone or more of the UV filters to be in encapsulated form. It isadvantageous here for the capsules to be so small that they cannot beviewed with the naked eye. In order to achieve the above-mentionedeffects, it is furthermore necessary for the capsules to be sufficientlystable and the encapsulated active ingredient (UV filter) only to bereleased to the environment to a small extent, or not at all.

[0096] Suitable capsules can have walls of inorganic or organicpolymers. For example, U.S. Pat. No. 6,242,099 B1 describes theproduction of suitable capsules with walls of chitin, chitin derivativesor polyhydroxylated polyamines. Capsules which can particularlypreferably be employed in accordance with the invention have walls whichcan be obtained by sol-gel processes, as described in the applicationsWO 00/09652, WO 00/72806 and WO 00/71084. Preference is again given hereto capsules whose walls are built up from silica gel (silica; undefinedsilicon oxide hydroxide). The production of corresponding capsules isknown to the person skilled in the art, for example from the citedpatent applications, whose contents expressly also belong to thesubject-matter of the present application.

[0097] The capsules in compositions according to the invention arepreferably present in amounts which ensure that the encapsulated UVfilters are present in the composition in the above-indicated amounts.

[0098] The compositions according to the invention may in additioncomprise further conventional skin-protecting or skin-care activeingredients. These may in principle be any active ingredients known tothe person skilled in the art.

[0099] Particularly preferred active ingredients arepyrimidinecarboxylic acids and/or aryl oximes.

[0100] Pyrimidinecarboxylic acids occur in halophilic microorganisms andplay a role in osmoregulation of these organisms (E. A. Galinski et al.,Eur. J. Biochem., 149 (1985) pages 135-139). Of the pyrimidinecarboxylicacids, particular mention should be made here of ectoin((S)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) andhydroxyectoin((S,S)-1,4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylicacid) and derivatives thereof. These compounds stabilize enzymes andother biomolecules in aqueous solutions and organic solvents.Furthermore, they stabilize, in particular, enzymes against denaturingconditions, such as salts, extreme pH values, surfactants, urea,guanidinium chloride and other compounds.

[0101] Ectoin and ectoin derivatives, such as hydroxyectoin, canadvantageously be employed in medicaments. In particular, hydroxyectoincan be employed for the preparation of a medicament for the treatment ofskin diseases. Other areas of application of hydroxyectoin and otherectoin derivatives are typically in areas in which, for example,trehalose is used as additive. Thus, ectoin derivatives, such ashydroxyectoin, can be used as protectant in dried yeast and bacteriacells. Pharmaceutical products, such as nonglycosylated,pharmaceutically active peptides and proteins, for example t-PA, canalso be protected with ectoin or its derivatives.

[0102] Of the cosmetic applications, particular mention should be madeof the use of ectoin and ectoin derivatives for the care of aged, dry orirritated skin. Thus, European Patent Application EP-A-0 671 161describes, in particular, that ectoin and hydroxyectoin are employed incosmetic compositions, such as powders, soaps, surfactant-containingcleansing products, lipsticks, rouge, make-ups, care creams andsunscreen compositions.

[0103] Preference is given here to the use of a pyrimidinecarboxylicacid of the following formula II

[0104] in which R¹ is a radical H or C1-8-alkyl, R² is a radical H orC1-4-alkyl, and R³, R⁴, R⁵ and R⁶ are each, independently of oneanother, a radical from the group consisting of H, OH, NH₂ andC1-4-alkyl. Preference is given to the use of pyrimidinecarboxylic acidsin which R² is a methyl or ethyl group, and R¹ or R⁵ and R⁶ are H.Particular preference is given to the use of the pyrimidinecarboxylicacids ectoin ((S)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylicacid) and hydroxyectoin((S,S)-1,4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylicacid). The compositions according to the invention preferably comprisepyrimidinecarboxylic acids of this type in amounts of up to 15% byweight. The pyrimidinecarboxylic acids are preferably employed here inratios of from 100:1 to 1:100 with respect to the compounds of theformula I, with ratios in the range from 1:10 to 10:1 being particularlypreferred.

[0105] Of the aryl oximes, preference is given to the use of2-hydroxy-5-methyllaurophenone oxime, which is also known as HMLO, LPOor F5. Its suitability for use in cosmetic compositions is disclosed,for example, in DE-A-41 16 123. Preparations which comprise2-hydroxy-5-methyllaurophenone oxime are accordingly suitable for thetreatment of skin diseases which are accompanied by inflammation. It isknown that preparations of this type can be used, for example, for thetherapy of psoriasis, various forms of eczema, irritative and toxicdermatitis, UV dermatitis and further allergic and/or inflammatorydiseases of the skin and integumentary appendages. Compositionsaccording to the invention which, in addition to the compound of theformula I, additionally comprise an aryl oxime, preferably2-hydroxy-5-methyllaurophenone oxime, exhibit surprisinganti-inflammatory suitability. The preparations here preferably comprisefrom 0.01 to 10% by weight of the aryl oxime, it being particularlypreferred for the composition to comprise from 0.05 to 5% by weight ofaryl oxime.

[0106] All compounds or components which can be used in the compositionsare either known or are commercially available or can be synthesized byknown processes.

[0107] The one or more compounds of the formula I can be incorporatedinto cosmetic or dermatological compositions in the customary manner.Suitable compositions are those for external use, for example in theform of a cream, lotion or gel or as a solution which can be sprayedonto the skin. Suitable for internal use are administration forms suchas capsules, coated tablets, powders, tablet solutions or solutions.

[0108] Examples which may be mentioned of application forms of thecompositions according to the invention are: solutions, suspensions,emulsions, PIT emulsions, pastes, ointments, gels, creams, lotions,powders, soaps, surfactant-containing cleansing preparations, oils,aerosols and sprays. Examples of other application forms are sticks,shampoos and shower compositions. Any desired customary excipients,auxiliaries and, if desired, further active ingredients may be added tothe composition.

[0109] Preferred auxiliaries originate from the group consisting ofpreservatives, antioxidants, stabilizers, solubilizers, vitamins,colorants and odor improvers.

[0110] Ointments, pastes, creams and gels may comprise the customaryexcipients, for example animal and vegetable fats, waxes, paraffins,starch, tragacanth, cellulose derivatives, polyethylene glycols,silicones, bentonites, silica, talc and zinc oxide, or mixtures of thesesubstances.

[0111] Powders and sprays may comprise the customary excipients, forexample lactose, talc, silica, aluminum hydroxide, calcium silicate andpolyamide powder, or mixtures of these substances. Sprays mayadditionally comprise the customary propellants, for examplechlorofluorocarbons, propane/butane or dimethyl ether.

[0112] Solutions and emulsions may comprise the customary excipients,such as solvents, solubilizers and emulsifiers, for example water,ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol,benzyl benzoate, propylene glycol, 1,3-butyl glycol, oils, in particularcottonseed oil, peanut oil, wheatgerm oil, olive oil, castor oil andsesame oil, glycerol fatty acid esters, polyethylene glycols and fattyacid esters of sorbitan, or mixtures of these substances.

[0113] Suspensions may comprise the customary excipients, such as liquiddiluents, for example water, ethanol or propylene glycol, suspendingagents, for example ethoxylated isostearyl alcohols, polyoxyethylenesorbitol esters and polyoxyethylene sorbitan esters, microcrystallinecellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth,or mixtures of these substances.

[0114] Soaps may comprise the customary excipients, such as alkali metalsalts of fatty acids, salts of fatty acid monoesters, fatty acid proteinhydrolysates, isethionates, lanolin, fatty alcohol, vegetable oils,plant extracts, glycerol, sugars, or mixtures of these substances.

[0115] Surfactant-containing cleansing products may comprise thecustomary excipients, such as salts of fatty alcohol sulfates, fattyalcohol ether sulfates, sulfosuccinic acid monoesters, fatty acidprotein hydrolysates, isethionates, imidazolinium derivatives, methyltaurates, sarcosinates, fatty acid amide ether sulfates,alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty aciddiethanolamides, vegetable and synthetic oils, lanolin derivatives,ethoxylated glycerol fatty acid esters, or mixtures of these substances.

[0116] Face and body oils may comprise the customary excipients, such assynthetic oils, such as fatty acid esters, fatty alcohols, siliconeoils, natural oils, such as vegetable oils and oily plant extracts,paraffin oils or lanolin oils, or mixtures of these substances.

[0117] Further typical cosmetic application forms are also lipsticks,lip-care sticks, mascara, eyeliner, eye-shadow, rouge, powder make-up,emulsion make-up and wax make-up, and sunscreen, pre-sun and after-suncompositions.

[0118] The preferred composition forms according to the inventioninclude, in particular, emulsions.

[0119] Emulsions according to the invention are advantageous andcomprise, for example, the said fats, oils, waxes and other fattysubstances, as well as water and an emulsifier, as usually used for apreparation of this type.

[0120] The lipid phase may advantageously be selected from the followinggroup of substances:

[0121] mineral oils, mineral waxes;

[0122] oils, such as triglycerides of capric or caprylic acid,furthermore natural oils, such as, for example, castor oil;

[0123] fats, waxes and other natural and synthetic fatty substances,preferably esters of fatty acids with alcohols having a low carbonnumber, for example with isopropanol, propylene glycol or glycerol, oresters of fatty alcohols with alkanoic acids having a low carbon numberor with fatty acids;

[0124] silicone oils, such as dimethylpolysiloxanes,diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof.

[0125] For the purposes of the present invention, the oil phase of theemulsions, oleogels or hydrodispersions or lipodispersions isadvantageously selected from the group consisting of esters of saturatedand/or unsaturated, branched and/or unbranched alkanecarboxylic acidshaving a chain length of from 3 to 30 carbon atoms and saturated and/orunsaturated, branched and/or unbranched alcohols having a chain lengthof from 3 to 30 carbon atoms, or from the group consisting of esters ofaromatic carboxylic acids and saturated and/or unsaturated, branchedand/or unbranched alcohols having a chain length of from 3 to 30 carbonatoms. Ester oils of this type can then advantageously be selected fromthe group consisting of isopropyl myristate, isopropyl palmitate,isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate,n-decyl oleate, isooctyl stearate, isononyl stearate, isononylisononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecylstearate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyloleate, erucyl erucate and synthetic, semi-synthetic and naturalmixtures of esters of this type, for example jojoba oil.

[0126] The oil phase may furthermore advantageously be selected from thegroup consisting of branched and unbranched hydrocarbons and waxes,silicone oils, dialkyl ethers, or the group consisting of saturated andunsaturated, branched and unbranched alcohols, and fatty acidtriglycerides, specifically the triglycerol esters of saturated and/orunsaturated, branched and/or unbranched alkanecarboxylic acids having achain length of from 8 to 24, in particular 12-18, carbon atoms. Thefatty acid triglycerides may advantageously be selected, for example,from the group consisting of synthetic, semi-synthetic and natural oils,for example olive oil, sunflower oil, soya oil, peanut oil, rapeseedoil, almond oil, palm oil, coconut oil, palm kernel oil and the like.

[0127] Any desired mixtures of oil and wax components of this type mayalso advantageously be employed for the purposes of the presentinvention. It may also be advantageous to employ waxes, for examplecetyl palmitate, as the only lipid component of the oil phase.

[0128] The oil phase is advantageously selected from the groupconsisting of 2-ethylhexyl isostearate, octyldodecanol, isotridecylisononanoate, isoeicosane, 2-ethylhexyl cocoate, C₁₂₋₁₅-alkyl benzoate,caprylic/capric acid triglyceride and dicapryl ether.

[0129] Particularly advantageous are mixtures of C₁₂₋₁₅-alkyl benzoateand 2-ethylhexyl isostearate, mixtures of C₁₂₋₁₅-alkyl benzoate andisotridecyl isononanoate, as well as mixtures of C₁₂₋₁₅-alkyl benzoate,2-ethylhexyl isostearate and isotridecyl isononanoate.

[0130] Of the hydrocarbons, paraffin oil, squalane and squalene mayadvantageously be used for the purposes of the present invention.

[0131] Furthermore, the oil phase may also advantageously have a contentof cyclic or linear silicone oils or consist entirely of oils of thistype, although it is preferred to use an additional content of otheroil-phase components in addition to the silicone oil or the siliconeoils.

[0132] The silicone oil to be used in accordance with the invention isadvantageously cyclomethicone (octamethylcyclotetrasiloxane). However,it is also advantageous for the purposes of the present invention to useother silicone oils, for example hexamethylcyclotrisiloxane,polydimethylsiloxane or poly(methylphenylsiloxane).

[0133] Also particularly advantageous are mixtures of cyclomethicone andisotridecyl isononanoate and of cyclomethicone and 2-ethylhexylisostearate.

[0134] The aqueous phase of the compositions according to the inventionoptionally advantageously comprises alcohols, diols or polyols having alow carbon number, and ethers thereof, preferably ethanol, isopropanol,propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethylor monobutyl ether, propylene glycol monomethyl, monoethyl or monobutylether, diethylene glycol monomethyl or monoethyl ether and analogousproducts, furthermore alcohols having a low carbon number, for exampleethanol, isopropanol, 1,2-propanediol or glycerol, and, in particular,one or more thickeners, which may advantageously be selected from thegroup consisting of silicon dioxide, aluminum silicates, polysacharidesand derivatives thereof, for example hyaluronic acid, xanthan gum,hydroxypropylmethylcellulose, particularly advantageously from the groupconsisting of the polyacrylates, preferably a polyacrylate from thegroup consisting of the so-called Carbopols, for example Carbopol grades980, 981, 1382, 2984 or 5984, in each case individually or incombination.

[0135] In particular, mixtures of the above-mentioned solvents are used.In the case of alcoholic solvents, water may be a further constituent.

[0136] Emulsions according to the invention are advantageous andcomprise, for example, the said fats, oils, waxes and other fattysubstances, as well as water and an emulsifier, as usually used for aformulation of this type.

[0137] In a preferred embodiment, the compositions according to theinvention comprise hydrophilic surfactants.

[0138] The hydrophilic surfactants are preferably selected from thegroup consisting of the alkylglucosides, acyl lactylates, betaines andcoconut amphoacetates.

[0139] The alkylglucosides are themselves advantageously selected fromthe group consisting of the alkylgluosides which are distinguished bythe structural formula

[0140] where R is a branched or unbranched alkyl radical having from 4to 24 carbon atoms, and where {overscore (DP)} denotes a mean degree ofglucosylation of up to 2.

[0141] The value {overscore (DP)} represents the degree of glucosidationof the alkylglucosides used in accordance with the invention and isdefined as$\overset{\_}{DP} = {{{\frac{p_{1}}{100} \cdot 1} + {\frac{p_{2}}{100} \cdot 2} + {\frac{p_{3}}{100} \cdot 3} + \ldots} = {\sum\limits_{\quad}^{\quad}\quad {\frac{p_{i}}{100} \cdot i}}}$

[0142] in which p₁, p₂, p₃ . . . p_(i) represent the proportion ofmono-, di-, tri- . . . i-fold glucosylated products in percent byweight. Advantageous according to the invention are products havingdegrees of glucosylation of 1-2, particularly advantageously of from 1.1to 1.5, very particularly advantageously of 1.2-1.4, in particular of1.3.

[0143] The value DP takes into account the fact that alkylglucosides aregenerally, as a consequence of their preparation, in the form ofmixtures of mono- and oligoglucosides. A relatively high content ofmonoglucosides, typically in the order of 40-70% by weight, isadvantageous in accordance with the invention.

[0144] Alkylglycosides which are particularly advantageously used forthe purposes of the invention are selected from the group consisting ofoctyl glucopyranoside, nonyl glucopyranoside, decyl glucopyranoside,undecyl glucopyranoside, dodecyl glucopyranoside, tetradecylglucopyranoside and hexadecyl glucopyranoside.

[0145] It is likewise advantageous to employ natural or synthetic rawmaterials and auxiliaries or mixtures which are distinguished by aneffective content of the active ingredients used in accordance with theinvention, for example Plantaren® 1200 (Henkel KGaA), Oramix® NS 10(Seppic).

[0146] The acyllactylates are themselves advantageously selected fromthe group consisting of the substances which are distinguished by thestructural formula

[0147] where R¹ is a branched or unbranched alkyl radical having from 1to 30 carbon atoms, and M⁺ is selected from the group consisting of thealkali metal ions and the group consisting of ammonium ions which aresubstituted by one or more alkyl and/or one or more hydroxyalkylradicals, or corresponds to half an equivalent of an alkaline earthmetal ion.

[0148] For example, sodium isostearyl lactylate, for example the productPathionic® ISL from the American Ingredients Company, is advantageous.

[0149] The betaines are advantageously selected from the groupconsisting of the substances which are distinguished by the structuralformula

[0150] where R² is a branched or unbranched alkyl radical having from 1to 30 carbon atoms.

[0151] R² is particularly advantageously a branched or unbranched alkylradical having from 6 to 12 carbon atoms.

[0152] For example, capramidopropylbetaine, for example the productTego® Betain 810 from Th. Goldschmidt A G, is advantageous.

[0153] A coconut amphoacetate which is advantageous for the purposes ofthe invention is, for example, sodium coconut amphoacetate, as availableunder the name Miranol® Ultra C32 from Miranol Chemical Corp.

[0154] The compositions according to the invention are advantageouslycharacterized in that the hydrophilic surfactant(s) is (are) present inconcentrations of 0.01-20% by weight, preferably 0.05-10% by weight,particularly preferably 0.1-5% by weight, in each case based on thetotal weight of the composition.

[0155] For use, the cosmetic and dermatological compositions accordingto the invention are applied to the skin and/or the hair in an adequateamount in the usual manner for cosmetics.

[0156] Cosmetic and dermatological compositions according to theinvention may exist in various forms. Thus, they may be, for example, asolution, a water-free composition, an emulsion or microemulsion of thewater-in-oil (W/O) or oil-in-water (O/W) type, a multiple emulsion, forexample of the water-in-oil-in-water (W/O/W) type, a gel, a solid stick,an ointment or an aerosol. It is also advantageous to administer ectoinsin encapsulated form, for example in collagen matrices and otherconventional encapsulation materials, for example as celluloseencapsulations, in gelatine, wax matrices or liposomally encapsulated.In particular, wax matrices, as described in DE-A 43 08 282, have provenfavorable. Preference is given to emulsions. O/W emulsions areparticularly preferred. Emulsions, W/O emulsions and O/W emulsions areobtainable in a conventional manner.

[0157] Emulsifiers that can be used are, for example, the known W/O andO/W emulsifiers. It is advantageous to use further conventionalco-emulsifiers in the preferred O/W emulsions according to theinvention.

[0158] Co-emulsifiers which are advantageous according to the inventionare, for example, O/W emulsifiers, principally from the group consistingof the substances having HLB values of 11-16, very particularlyadvantageously having HLB values of 14.5-15.5, so long as the O/Wemulsifiers have saturated radicals R and R′. If the O/W emulsifiershave unsaturated radicals R and/or R′ or in the case of isoalkylderivatives, the preferred HLB value of such emulsifiers may also belower or higher.

[0159] It is advantageous to select the fatty alcohol ethoxylates fromthe group consisting of ethoxylated stearyl alcohols, cetyl alcohols,cetylstearyl alcohols (cetearyl alcohols). Particular preference isgiven to the following: polyethylene glycol (13) stearyl ether(steareth-13), polyethylene glycol (14) stearyl ether (steareth-14),polyethylene glycol (15) stearyl ether (steareth-15), polyethyleneglycol (16) stearyl ether (steareth-16), polyethylene glycol (17)stearyl ether (steareth-17), polyethylene glycol (18) stearyl ether(steareth-18), polyethylene glycol (19) stearyl ether (steareth-19),polyethylene glycol (20) stearyl ether (steareth-20), polyethyleneglycol (12) isostearyl ether (isosteareth-12), polyethylene glycol (13)isostearyl ether (isosteareth-13), polyethylene glycol (14) isostearylether (isosteareth-14), polyethylene glycol (15) isostearyl ether(isosteareth-15), polyethylene glycol (16) isostearyl ether(isosteareth-16), polyethylene glycol (17) isostearyl ether(isosteareth-17), polyethylene glycol (18) isostearyl ether(isosteareth-18), polyethylene glycol (19) isostearyl ether(isosteareth-19), polyethylene glycol (20) isostearyl ether(isosteareth-20), polyethylene glycol (13) cetyl ether (ceteth-13),polyethylene glycol (14) cetyl ether (ceteth-14), polyethylene glycol(15) cetyl ether (ceteth-15), polyethylene glycol (16) cetyl ether(ceteth16), polyethylene glycol (17) cetyl ether (ceteth-17),polyethylene glycol (18) cetyl ether (ceteth-18), polyethylene glycol(19) cetyl ether (ceteth-19), polyethylene glycol (20) cetyl ether(ceteth-20), polyethylene glycol (13) isocetyl ether (isoceteth-13),polyethylene glycol (14) isocetyl ether (isoceteth-14), polyethyleneglycol (15) isocetyl ether (isoceteth-15), polyethylene glycol (16)isocetyl ether (isoceteth-16), polyethylene glycol (17) isocetyl ether(isoceteth-17), polyethylene glycol (18) isocetyl ether (isoceteth-18),polyethylene glycol (19) isocetyl ether (isoceteth-19), polyethyleneglycol (20) isocetyl ether (isoceteth-20), polyethylene glycol (12)oleyl ether (oleth-12), polyethylene glycol (13) oleyl ether (oleth-13),polyethylene glycol (14) oleyl ether (oleth-14), polyethylene glycol(15) oleyl ether (oleth-15), polyethylene glycol (12) lauryl ether(laureth-12), polyethylene glycol (12) isolauryl ether (isolaureth-12),polyethylene glycol (13) cetylstearyl ether (ceteareth-13), polyethyleneglycol (14) cetylstearyl ether (ceteareth-14), polyethylene glycol (15)cetylstearyl ether (ceteareth-15), polyethylene glycol (16) cetylstearylether (ceteareth-16), polyethylene glycol (17) cetylstearyl ether(ceteareth-17), polyethylene glycol (18) cetylstearyl ether(ceteareth-18), polyethylene glycol (19) cetylstearyl ether(ceteareth-19), polyethylene glycol (20) cetylstearyl ether(ceteareth-20).

[0160] It is furthermore advantageous to select the fatty acidethoxylates from the following group:

[0161] polyethylene glycol (20) stearate, polyethylene glycol (21)stearate, polyethylene glycol (22) stearate, polyethylene glycol (23)stearate, polyethylene glycol (24) stearate, polyethylene glycol (25)stearate, polyethylene glycol (12) isostearate, polyethylene glycol (13)isostearate, polyethylene glycol (14) isostearate, polyethylene glycol(15) isostearate, polyethylene glycol (16) isostearate, polyethyleneglycol (17) isostearate, polyethylene glycol (18) isostearate,polyethylene glycol (19) isostearate, polyethylene glycol (20)isostearate, polyethylene glycol (21) isostearate, polyethylene glycol(22) isostearate, polyethylene glycol (23) isostearate, polyethyleneglycol (24) isostearate, polyethylene glycol (25) isostearate,polyethylene glycol (12) oleate, polyethylene glycol (13) oleate,polyethylene glycol (14) oleate, polyethylene glycol (15) oleate,polyethylene glycol (16) oleate, polyethylene glycol (17) oleate,polyethylene glycol (18) oleate, polyethylene glycol (19) oleate,polyethylene glycol (20) oleate.

[0162] The ethoxylated alkyl ether carboxylic acid or salt thereof usedcan advantageously be sodium laureth-11 carboxylate. An alkyl ethersulfate which can advantageously be used is sodium laureth-14 sulfate.An ethoxylated cholesterol derivative which can advantageously be usedis polyethylene glycol (30) cholesteryl ether. Polyethylene glycol (25)soyasterol has also proven successful. Ethoxylated triglycerides whichcan advantageously be used are the polyethylene glycol (60) eveningprimrose glycerides.

[0163] It is furthermore advantageous to select the polyethylene glycolglycerol fatty acid esters from the group consisting of polyethyleneglycol (20) glyceryl laurate, polyethylene glycol (21) glyceryl laurate,polyethylene glycol (22) glyceryl laurate, polyethylene glycol (23)glyceryl laurate, polyethylene glycol (6) glyceryl caprate/caprinate,polyethylene glycol (20) glyceryl oleate, polyethylene glycol (20)glyceryl isostearate, polyethylene glycol (18) glyceryl oleate/cocoate.

[0164] It is likewise favorable to select the sorbitan esters from thegroup consisting of polyethylene glycol (20) sorbitan monolaurate,polyethylene glycol (20) sorbitan monostearate, polyethylene glycol (20)sorbitan monoisostearate, polyethylene glycol (20) sorbitanmonopalmitate, polyethylene glycol (20) sorbitan monooleate.

[0165] Optional W/O emulsifiers, but ones which may nevertheless beadvantageous for the purposes of the invention are the following:

[0166] fatty alcohols having from 8 to 30 carbon atoms, monoglycerolesters of saturated and/or unsaturated, branched and/or unbranchedalkanecarboxylic acids having a chain length of from 8 to 24 carbonatoms, in particular 12-18 carbon atoms, diglycerol esters of saturatedand/or unsaturated, branched and/or unbranched alkanecarboxylic acidshaving a chain length of from 8 to 24 carbon atoms, in particular 12-18carbon atoms, monoglycerol ethers of saturated and/or unsaturated,branched and/or unbranched alcohols having a chain length of from 8 to24 carbon atoms, in particular 12-18 carbon atoms, diglycerol ethers ofsaturated and/or unsaturated, branched and/or unbranched alcohols havinga chain length of from 8 to 24 carbon atoms, in particular 12-18 carbonatoms, propylene glycol esters of saturated and/or unsaturated, branchedand/or unbranched alkanecarboxylic acids having a chain length of from 8to 24 carbon atoms, in particular 12-18 carbon atoms, and sorbitanesters of saturated and/or unsaturated, branched and/or unbranchedalkanecarboxylic acids having a chain length of from 8 to 24 carbonatoms, in particular 12-18 carbon atoms.

[0167] Particularly advantageous W/O emulsifiers are glycerylmonostearate, glyceryl monoisostearate, glyceryl monomyristate, glycerylmonooleate, diglyceryl monostearate, diglyceryl monoisostearate,propylene glycol monostearate, propylene glycol monoisostearate,propylene glycol monocaprylate, propylene glycol monolaurate, sorbitanmonoisostearate, sorbitan monolaurate, sorbitan monocaprylate, sorbitanmonoisooleate, sucrose distearate, cetyl alcohol, stearyl alcohol,arachidyl alcohol, behenyl alcohol, isobehenyl alcohol, selachylalcohol, chimyl alcohol, polyethylene glycol (2) stearyl ether(steareth-2), glyceryl monolaurate, glyceryl monocaprinate and glycerylmonocaprylate.

[0168] Preferred compositions according to the invention areparticularly suitable for protecting human skin against ageing processesand against oxidative stress, i.e. against damage caused by freeradicals, as are produced, for example, by solar irradiation, heat orother influences. In this connection, it is in the variousadministration forms usually used for this application. For example, itmay, in particular, be in the form of a lotion or emulsion, such as inthe form of a cream or milk (O/W, W/O, O/W/O, W/O/W), in the form ofoily-alcoholic, oily-aqueous or aqueous-alcoholic gels or solutions, inthe form of solid sticks or may be formulated as an aerosol.

[0169] The composition may comprise cosmetic adjuvants which are usuallyused in this type of composition, such as, for example, thickeners,softeners, moisturizers, surface-active agents, emulsifiers,preservatives, antifoams, perfumes, waxes, lanolin, propellants, dyesand/or pigments which color the composition itself or the skin, andother ingredients usually used in cosmetics.

[0170] The dispersant or solubilizer used can be an oil, wax or otherfatty substance, a lower monoalcohol or lower polyol or mixturesthereof. Particularly preferred monoalcohols or polyols include ethanol,isopropanol, propylene glycol, glycerol and sorbitol.

[0171] A preferred embodiment of the invention is an emulsion in theform of a protective cream or milk which, apart from the compound(s) ofthe formula I, comprises, for example, fatty alcohols, fatty acids,fatty acid esters, in particular triglycerides of fatty acids, lanolin,natural and synthetic oils or waxes and emulsifiers in the presence ofwater.

[0172] Further preferred embodiments are oily lotions based on naturalor synthetic oils and waxes, lanolin, fatty acid esters, in particulartriglycerides of fatty acids, or oily-alcoholic lotions based on a loweralcohol, such as ethanol, or a glycerol, such as propylene glycol,and/or a polyol, such as glycerol, and oils, waxes and fatty acidesters, such as triglycerides of fatty acids.

[0173] The preparation according to the invention may also be in theform of an alcoholic gel which comprises one or more lower alcohols orpolyols, such as ethanol, propylene glycol or glycerol, and a thickener,such as siliceous earth. The oily-alcoholic gels also comprise naturalor synthetic oil or wax.

[0174] The solid sticks consist of natural or synthetic waxes and oils,fatty alcohols, fatty acids, fatty acid esters, lanolin and other fattysubstances.

[0175] If a composition is formulated as an aerosol, the customarypropellants, such as alkanes, fluoroalkanes and chlorofluoroalkanes, aregenerally used.

[0176] The cosmetic composition may also be used to protect the hairagainst photochemical damage in order to prevent color changes,bleaching or damage of a mechanical nature. In this case, a suitableformulation is in the form of a rinse-out shampoo, lotion, gel oremulsion, the composition in question being applied before or aftershampooing, before or after coloring or bleaching or before or afterpermanent waving. It is also possible to select a composition in theform of a lotion or gel for styling or treating the hair, in the form ofa lotion or gel for brushing or blow-waving, in the form of a hairlacquer, permanent waving composition, colorant or bleach for the hair.Besides the compounds of the formula I, the composition havinglight-protection properties may comprise various adjuvants used in thistype of composition, such as surfactants, thickeners, polymers,softeners, preservatives, foam stabilizers, electrolytes, organicsolvents, silicone derivatives, oils, waxes, antigrease agents, dyesand/or pigments which color the composition itself or the hair, or otheringredients usually used for hair care.

[0177] The present invention furthermore relates to a process for thecomposition of a preparation which is characterized in that at least onecompound of the formula I having radicals as described above is mixedwith an excipient which is suitable cosmetically or dermatologically orfor foods, and to the use of a compound of the formula I for thepreparation of a composition having antioxidant properties.

[0178] The compositions according to the invention can be prepared usingtechniques which are well known to the person skilled in the art.

[0179] The mixing can result in dissolution, emulsification ordispersion of the compound of the formula I in the excipient.

[0180] In a process which is preferred in accordance with the invention,the compound of the formula I is prepared by reacting a2-hydroxyacetophenone compound with a lithium compound and subsequentlywith a keto compound.

[0181] For example, as described by M. Cushman and D. Nagarathnam in:Tetrahedron Letters, 31, 6497-6500, 1990 and M. Cushman; D. Nagarathnam;Journal of Organic Chemistry, 56, 4884-4887, 1991, the phenolic hydroxylgroups can be deprotonated using a large excess of lithiumbis(trimethylsilyl)amide under homogeneous reaction conditions in orderto prepare the lithium enolate of the corresponding ketone. The carbonatom of the lithium enolate can subsequently be acylatedregioselectively using an aroyl chloride to give a β-diketoneintermediate directly, which is subsequently cyclized in the acidicmedium. However, this process has the disadvantage of the large excessof lithium base, which can only be removed with difficulty, even in aplurality of purification steps, and the high price of the lithium base.

[0182] It is therefore particularly preferred to carry out a process asdescribed in the international patent application WO 00/60889. In thisprocess, which is preferred in accordance with the invention, the ratiobetween the molar equivalents of lithium compound and the molarequivalents of 2-hydroxyacetophenone compound functional groups to bemetallated is selected in the range from 1 to 1.2.

[0183] Surprisingly, it has been found that the above-mentioned ratioallows complete metallation of all hydroxyl groups and the carbonylgroup of the 2-hydroxyacetophenone compound. A ratio of less than 1would result in incomplete metallation and thus in a large number ofundesired by-products. A ratio of more than 1.2, by contrast, means theuse of a larger amount of the lithium compounds, which are usually notinexpensive, and the entrainment of lithium compounds in all furthersubsequent steps, in particular purification steps.

[0184] The lithium compound is preferably selected from inorganiclithium compounds, since they are available inexpensively and readily inlarge amounts. Furthermore, they offer the advantage that they aresparingly soluble to insoluble in organic solvents, meaning that, ifemployed in excess, they can easily be filtered out of the reactionmixture after a metallation reaction carried out under heterogeneousconditions.

[0185] In a preferred embodiment of the process according to theinvention, the ratio between the lithium compound and the2-hydroxyacetophenone compound functional groups to be metallated isprecisely 1. It is thus achieved that no lithium compounds that maystill be dissolved occur as impurities in the end product, since theseusually cannot be removed from the intermediates and end products, evenby purification steps, such as recrystallization.

[0186] The metallation is advantageously carried out in an etherealsolvent, since this supports the metallation reaction through itspolarity through the formation of Li solvates, increasing the basicityof the lithium base.

[0187] The 2-hydroxyacetophenone employed in the process according tothe invention preferably has the following structure:

[0188] where R¹ to R⁴ and R⁸ are as defined above or are groups whichcan be converted into groups as defined above by chemical modifications,such as, for example, removal of protecting groups, oxidation orreduction.

[0189] The keto compound for carrying out the process according to theinvention preferably has the following structure:

[0190] where R⁵ to R⁷ and R⁹ to R¹⁰ are as defined above or are groupswhich can be converted into groups as defined above by chemicalmodifications, such as, for example, removal of protecting groups,oxidation or reduction, and where R^(y) can be a halide, alkoxy or estergroup.

[0191] The hydroxyl groups of the 2-hydroxyacetophenone compound arepreferably not protected. Complex reactions for introduction and removalof protecting groups are thus avoided, enabling the reaction to proceedparticularly simply.

[0192] In the case of the keto compounds, R^(y) is chloride, i.e. thecompound is an acid chloride, an alkoxy group, i.e. the compound is anester, or an ester group, i.e. the compound is an acid anhydride. Theuse of different groups also enables variation and precise selection ofthe reaction time, depending on the substrate employed. For example, thereaction time on use of an acid chloride or acid anhydride is between 2and 6 hours, usually between 4 and 5 hours. On use of an ester or on useof silylated protecting groups, the reaction time is more than 8 hours,usually more than 10 hours, but often also about 16-20 hours.

[0193] Firstly, the 2-hydroxyacetophenone compound is preferablycondensed with the ketone and a lithium compound in dry THF at lowtemperatures (from −78° C. to −50° C.), giving a stable diketoneintermediate. At temperatures above −50° C., the reaction either doesnot proceed at all or does so too quickly, i.e. with undesiredby-products or alternatively with decomposition of the startingmaterial, so that the range from −78° C. to −50° C. is preferred. Thediketone is subsequently cyclized at 95-100° C. under acidic conditions,to give a flavone derivative.

[0194] Particularly suitable lithium bases which are used in the processaccording to the invention are the lithium bases listed below:

[0195] LiNH₂, LiN(CH₃)₂, LiN(C₂H₅)₂, LiNCH(CH₃)₂ (LDA), Me₃CLi, PhCH₂Li,Ph₂CHLi, Ph₃CLi, LiCN, LiC(NO₃)₃, LiC(CN)₃, LiN(C₆H₁₁)₂, LiN(CH₂)₂,LiCH₃, LiC₂H₅, LiCH(CH₃)₂, LiC₄H₉, LiCH₂CH(CH₃)₂, LiC₆H₁₃, LiPh,LICH₃COCHCOCH₃, LiClO, LiClO₄, LiIO₄, Li₂O, LiOH, LiOCH₃, LiOC₂H₅,LiOC₄H₉, LiOPh, LiOOCOPh, lithium enolates of the general formulaLiOCR═CR′₂, where R and R′ are aliphatic or aromatic radicals,LiOSi(CH₃)₃, Li(Si(CH₃)₃)₂, Li₂CO₃ or lithium2,2,6,6-tetramethylpiperidine (LiTMP).

[0196] As described above, particular preference amongst these is givento the purely inorganic lithium compounds or the lithium compounds whoseusually organic radical is bonded to the lithium atom via inorganicatoms (O, N, Si).

[0197] The solvent for carrying out the metallation reaction is, asdescribed above, preferably an ethereal solvent, for example diethylether, tetrahydrofuran (THF) or dibutyl ether. However, other polarsolvents, such as methyl ethyl ketone and the like, may likewise beused, but also, depending on the hydroxyacetophenone employed, nonpolarsolvents, such as, for example, n-hexane, heptane, benzene, toluene,etc.

[0198] It has also been noted that compounds of the formula I can have astabilising effect on the composition. When used in correspondingproducts, the latter are thus also stable for longer and do not changetheir appearance. In particular, the effectiveness of the ingredients,for example vitamins, is retained even in the case of application overextended periods or extended storage. This is, inter alia, particularlyadvantageous in the case of compositions for protecting the skin againstthe effect of UV rays since these cosmetics are exposed to particularlyhigh stresses by UV radiation.

[0199] The positive effects of compounds of the formula I give rise totheir particular suitability for use in cosmetic or pharmaceuticalcompositions.

[0200] The properties of compounds of the formula I should likewise beregarded as positive for use in foods or as food supplements or asfunctional foods. The further explanations given for foods also applycorrespondingly to food supplements and functional foods.

[0201] The foods which can be enriched with one or more compounds of theformula I in accordance with the present invention include all materialswhich are suitable for consumption by animals or consumption by humans,for example vitamins and provitamins thereof, fats, minerals or aminoacids. (The foods may be solid, but also liquid, i.e. in the form of abeverage).

[0202] The present invention accordingly furthermore relates to the useof a compound of the formula I as food additive for human or animalnutrition, and compositions which are foods or food supplements andcomprise corresponding excipients.

[0203] Foods which can be enriched with one or more compounds of theformula I in accordance with the present invention are, for example,also foods which originate from a single natural source, such as, forexample, sugar, unsweetened juice, squash or puree of a single plantspecies, such as, for example, unsweetened apple juice (for example alsoa mixture of different types of apple juice), grapefruit juice, orangejuice, apple compote, apricot squash, tomato juice, tomato sauce, tomatopuree, etc. Further examples of foods which can be enriched with one ormore compounds of the formula I in accordance with the present inventionare corn or cereals from a single plant species and materials producedfrom plant species of this type, such as, for example, cereal syrup, ryeflour, wheat flour or oat bran. Mixtures of foods of this type are alsosuitable for being enriched with one or more compounds of the formula Iin accordance with the present invention, for example multivitaminpreparations, mineral mixtures or sweetened juice. As further examplesof foods which can be enriched with one or more compounds of the formulaI in accordance with the present invention, mention may be made of foodpreparations, for example prepared cereals, biscuits, mixed drinks,foods prepared especially for children, such as yoghurt, diet foods,low-calorie foods or animal feeds.

[0204] The foods which can be enriched with one or more compounds of theformula I in accordance with the present invention thus include alledible combinations of carbohydrates, lipids, proteins, inorganicelements, trace elements, vitamins, water or active metabolites ofplants and animals.

[0205] The foods which can be enriched with one or more compounds of theformula I in accordance with the present invention are preferablyadministered orally, for example in the form of meals, pills, tablets,capsules, powders, syrup, solutions or suspensions.

[0206] The foods according to the invention enriched with one or morecompounds of the formula I can be prepared using techniques which arewell known to the person skilled in the art.

[0207] Due to their action as antioxidants or free-radical scavengers,compounds of the formula I are also suitable as medicament ingredients.Here, they support or replace natural mechanisms which scavenge freeradicals in the body. The compounds of the formula I can in some casesbe compared in terms of their action with free-radical scavengers suchas vitamin C. Compounds of the formula I can be used, for example, forpreventative treatment of inflammation and allergies of the skin and incertain cases for preventing certain types of cancer. Compounds of theformula I are particularly suitable for the preparation of a medicamentfor the treatment of inflammation, allergies and irritation, inparticular of the skin. It is furthermore possible to preparemedicaments which act as a vein tonic, as an agent for increasing thestrength of blood capillaries, as cuperose inhibitor, as chemical,physical or actinic erythema inhibitor, as agent for the treatment ofsensitive skin, as decongestant, as desiccant, as slimming agent, asanti-wrinkle agent, as stimulator for the synthesis of components of theextracellular matrix, as strengthening agent for improving skinelasticity, and as anti-ageing agent. Furthermore, compounds of theformula I which are preferred in this connection exhibit antiallergicand anti-inflammatory and antiirritative actions. They are thereforesuitable for the preparation of medicaments for the treatment ofinflammation or allergic reactions.

[0208] The entire disclosure of all applications, patents andpublications, cited herein and of corresponding German application No.10244282.7, filed Sep. 23, 2002, is incorporated by reference herein.

[0209] The invention is explained in greater detail by means ofexamples. The invention can be carried out in throughout the rangeclaimed and is not restricted to the examples given here.

[0210] The preceding examples can be repeated with similar success bysubstituting the generically or specifically described reactants and/oroperating conditions of this invention for those used in the precedingexamples.

EXAMPLES

[0211] CHEMICAL SOURCE ART.NO. PURITY 2′,5′-Dihydroxyacetophenone MerckKGaA 818284  98% 2′,4′-Dihydroxyacetophenone Merck KGaA 822027  98%4-Methoxybenzoyl chloride Merck KGaA 820106  99% Lithium hydroxide MerckKGaA 105691  98% D-(+)-alpha-acetobromoglucose Merck KGaA 800121Tetra-n-butylammonium Merck KGaA 818839 bromide Sodium hydroxidesolution Merck KGaA 109137 1 N Boron tribromide Merck KGaA 801063  99%Sodium methoxide Merck KGaA 806538 Tetrahydrofuran Merck KGaA 108107SeccoSolv 0.0075% H₂O Dichloromethane Merck KGaA 10316049 ultrapureHydrochloric acid, fuming Merck KGaA 100314  37% Acetic acid Merck KGaA100056 100% Sulfuric acid Merck KGaA 100731 95-97%

Example 1 Preparation of 6,3′,4′-trihydroxyflavone

[0212]

[0213] Dry, pulverulent lithium hydroxide (19.7 mmol, 3 equivalents) isadded in one portion to a well-stirred solution of2′,5′-dihydroxyacetophenone (6.4 mmol) in dry THF (5 ml) at −78° C.under an argon atmosphere. The reaction mixture is stirred at −78° C.for one hour and subsequently at −10° C. for two hours. After re-coolingto −78° C., a solution of 3′,4-dimethoxybenzoyl chloride (6.5 mmol) inTHF (10 ml) is added in one portion. The mixture is stirred at −78° C.for one hour and at room temperature for 4 hours until the startingmaterial has disappeared. The reaction mixture is emptied onto a mixtureof ice (150 g) and concentrated HCl (5 ml) and extracted withdichloromethane (3×50 ml). The solvents are removed from the driedextracts, and the residue is dried under reduced pressure for 24 hours.Glacial acetic acid (30 ml) and sulfuric acid (0.2 ml) are added to theresidue, and the mixture is heated at 95-100° C. under an argonatmosphere for from 30 minutes to one hour. Approximately one third ofthe acetic acid is stripped off, and the residue is emptied into water.The precipitated product is filtered, washed and dried andrecrystallised from methanol. A boron tribromide solution (9.6 ml, 32equivalents) is added to a well-stirred solution of3′,4′-dimethoxy-6-hydroyflavone (6.4 mmol) in dichloromethane (100 ml)under an argon atmosphere at −78° C. When all the boron tribromidesolution has been added, the reaction mixture is stirred at roomtemperature for 24 hours and subsequently added to an ice/water mixture(300 ml). The product is filtered and recrystallised from ethanol/water,giving 6,3′,4′-trihydroxyflavone.

[0214]¹H NMR (DMSO-d⁶, 300 MHz) δ9.76 (very br s, 3H, exchanges withD₂O, OH on C-6, C-3′ and C-4′), 7.58 (d, 1H, ³J_(8,7)=, H-8), 7.42 (d,1H, ⁴J_(2,6)=, H-2′), 7.41 (dd, 1H, ³J_(6′,5′)=, ⁴J_(6′,2′)=, H-6′),7.31 (d, 1H, ⁴J_(5,7)=, H-5), 7.23 (dd, 1H, ³J_(7,8)=, ⁴J_(7,5)=, H-7),6.91 (d, H, ³J_(5′,6′)=, H-5), 6.68 (s, 1H, H-3).

[0215]¹³C NMR (DMSO-d⁶, 75.47 MHz) δ176.63 (C-4), 162.76 (C-2), 154.61(C-6), 149.14 (C-9 and C-3′), 145.61 (C-4′), 124.10 (C-1′), 122.63(C-7), 122.10 (C-10), 119.46 (C-6′), 118.55 (C-8), 115.88 (C-5′), 113.16(C-2′), 107.47 (C-5), 103.84 (C-3).

[0216] EI-MS m/e (% relative composition): 270 (100)

[0217] Anal. Calcd for C₁₅H₁₀O₅: C, 66.67%; H, 3.73%; O, 29.60%. Found:C, 65.4%; H, 3.9%; O, 30.1%.

[0218] UV-VIS (2-propanol, 1 mg/100 ml) λ_(min)=251-277 nm, λ_(max)=339nm.

Example 2 Preparation of 5,6,7-trihydroxyflavone

[0219]

[0220] Dry, pulverulent lithium hydroxide (38.7 mmol, 3 equivalents) isadded in one portion to a well-stirred solution of2′,4′,5′,6′-tetrahydroxyflavone (12.9 mmol) in dry THF (5 ml) at −78° C.under an argon atmosphere. The reaction mixture is stirred at −78° C.for one hour and subsequently at −10° C. for two hours. After re-coolingto −78° C., a solution of -benzoyl chloride (14.2 mmol) in THF (20 ml)is added in one portion. The mixture is stirred at −78° C. for one hourand at room temperature for 4 hours until the starting material hasdisappeared. The reaction mixture is emptied onto a mixture of ice (300g) and concentrated HCl (10 ml) and extracted with dichloromethane (3×50ml). The solvents are removed from the dried extracts, and the residueis dried under reduced pressure for 24 hours. Glacial acetic acid (100ml) and sulfuric acid (0.5 ml) are added to the residue, and the mixtureis heated at 95-100° C. under an argon atmosphere for from 30 minutes toone hour. Approximately one third of the acetic acid is stripped off,and the residue is emptied into water. The precipitated product isfiltered, washed and dried and recrystallised from methanol, giving5,6,7-trihydroxyflavone. M.p: 256-271° C.

[0221]¹H NMR (DMSO-d⁶, 500 MHz) δ12.67 (s, 1H, exchanges with D₂O, OH onC-5), 10.54 (br s, 1H, exchanges with D₂O, OH on C-7), 8.80 (br s, 1H,exchanges with D₂O, OH on C-6), 8.05 (d, 2H, ³J_(2′,3′)=³J_(6′,5′)=7.93,H-2′ and H-6), 7.57 (m, 3H, H-3′, H-4′ and H-5′), 6.92 (s, 1H, H-8),6.64 (s, 1H, H-3).

[0222]¹³C NMR (DMSO-d⁶, 62.90 MHz) δ182.05 (C-4), 162.85 (C-2), 153.59(C-7), 149.81 (C-9), 146.97 (C-5), 131.70 (C-4′), 130.92 (C-1′), 129.29(C-6), 129.00 (C3′and C-5′), 126.21 (C-2′ and C-6′), 104.43 (C-8),104.26 (C-10), 93.98 (C-3).

[0223] EI-MS m/e (% relative composition): 270 (100).

[0224] UV-vis (2-propanol, 1 mg/100 ml) λ_(min)=276.5 nmλ_(max)=325.5 nm

Example 3 Preparation of 7,8,3′,4′-tetrahydroxyflavone

[0225]

[0226] Dry, pulverulent lithium hydroxide (27.3 mmol, 4 equivalents) isadded in one portion to a well-stirred solution of2′,3′,4′-trihydroxyacetophenone (6.4 mmol) in dry THF (5 ml) at −78° C.under an argon atmosphere. The reaction mixture is stirred at −78° C.for one hour and subsequently at −10° C. for two hours. After re-coolingto −78° C., a solution of 3′,4-dimethoxybenzoyl chloride (6.5 mmol) inTHF (10 ml) is added in one portion. The mixture is stirred at −78° C.for one hour and at room temperature for 4 hours until the startingmaterial has disappeared. The reaction mixture is emptied onto a mixtureof ice (150 g) and concentrated HCl (5 ml) and extracted withdichloromethane (3×50 ml). The solvents are removed from the driedextracts, and the residue is dried under reduced pressure for 24 hours.Glacial acetic acid (30 ml) and sulfuric acid (0.2 ml) are added to theresidue, and the mixture is heated at 95-100° C. under an argonatmosphere for from 30 minutes to one hour. Approximately one third ofthe acetic acid is stripped off, and the residue is emptied into water.The precipitated product is filtered, washed and dried andrecrystallised from methanol. A boron tribromide solution (9.6 ml, 32equivalents) is added to a well-stirred solution of3′,4′-dimethoxy-7,8-dihydroyflavone (6.4 mmol) in dichloromethane (100ml) under an argon atmosphere at −78° C. When all the boron tribromidesolution has been added, the reaction mixture is stirred at roomtemperature for 24 hours and subsequently added to an ice/water mixture(300 ml). The product is filtered and recrystallised from ethanol/water,giving 7,8,3′,4′-tetrahydroxyflavone.

[0227]¹H NMR (DMSO-d⁶, 300 MHz) δ9.67 (br s, 4H, exchanges with D₂O, OHon C-7, C-8, C-3′ and C-4′), 7.59 (d, 1H, ⁴J_(2′,6′)=, H-2′), 7.47 (dd,1H, ³J_(6′,5′)=, ⁴J_(6′,2′)=, H-6′), 7.39 (d, 1H, ³J_(6,5)=, H-6), 6.93(d, 1H, ³J_(5,6)=, H-5′), 6.90 (d, 1H, ³J_(5′,6′)=, H-5′), 6.61 (S, 1H,H-3′).

[0228]¹³C NMR (DMSO-d⁶, 75.47 MHz) δ176.64 (C-4), 162.34 (C-2), 150.09(C-7), 149.00 (C-3′), 146.61 (C-9), 145.52 (C-4′), 133.04 (C-8), 122.30(C-1′), 118.61 (C-5), 116.87 (C-10), 115.80 (C-6′), 114.87 (C-5′),113.59 (C-2′), 113.33 (C-6), 103.82 (C-3).

[0229] EI-MS m/e (% relative abundance) composition: 286 (100)

[0230] UV-VIS (2-propanol, 1 mg/100 ml) λ_(min)=265-277 nm, λ_(max)=343nm.

[0231] Anal. Calcd for C₁₅H₁₀O₆: C, 62.94%; H, 3.52%; O, 33.54%. Found:C, 61.0%; H, 3.0%; O, 28.7%.

Example 4 Antioxidant Properties

[0232] The antioxidant activity of the compounds according to theinvention is determined compared with the activity of quercetin(3,5,7,3′,4′-pentahydroxyflavone) and other conventional antioxidants.The antioxidant activity here is taken to mean the ability to functionas hydrogen or electron donor and thus to be able to scavenge freeradicals. DPPH assay is used for the determination.

[0233] DPPH Assay

[0234] A stock solution of 2,2-diphenyl-1-picrylhydrazyl (DPPH) inethanol is prepared (0.025 g/l of DPPH-free radicals). Aliquots of thissolution are mixed with various concentrations of the compound to betested. The absorbance is in each case measured at 515 nm, 25° C. and 1cm.

[0235] As EC₅₀, the value is determined at which 50% of the originalDPPH free-radical concentration is still present. The lower this value,the higher the corresponding antioxidant activity.

[0236] The reaction time necessary to achieve this value is indicated inthe value T_(EC50) (in minutes).

[0237] The anti-free-radical efficiency (AE) is obtained from this inaccordance with the following relationship:${AE} = \frac{1}{{EC}_{50}T_{EC50}}$

[0238] A higher AE value here indicates a higher activity against freeradicals. TABLE 1 Results of the DPPH assay Compound EC₅₀ T_(EC50) AE(×10⁻³) 5,6,7-Trihydroxyflavone/bacalein 0.10 360 27.786,3′,4′-Trihydroxyflavone 0.12 180 46.30 7,8,3′,4′-Tetrahydroxyflavone0.09 600 18.52 3,5,7,3′,4′-Pentahydroxyflavanone/taxifolin 0.15 12005.53 3,5,7,3′,4′-Pentahydroxyflavone/quercetin 0.089 600 18.72Tocopherol 0.26 <60 64.1 Ascorbic acid 0.27 <60 61.72 Ferulic acid 0.34600 4.9

Example 5 Compositions

[0239] Formulations of cosmetic compositions which comprise compoundsaccording to Examples 1-3 are indicated by way of example below. Inaddition, the INCI names of the commercially available compounds areindicated.

[0240] UV Pearl, OMC is the preparation with the INCI name: Water (forEU: Aqua), Ethylhexyl Methoxycinnamate, Silica, PVP, Chlorphenesin, BHT;this preparation is commercially available under the name Eusolex®UVPearl™OMC from Merck KGaA, Darmstadt.

[0241] The other UV Pearl products indicated in the tables each have ananalogous composition with OMC replaced by the UV filters indicated.TABLE 1 W/O emulsions (data in % by weight) 1-1 1-2 1-3 1-4 1-5 1-6 1-71-8 1-9 1-10 Titanium Dioxide 2 5 3 6,3′,4′- 5 3 2 1 2 1 1Trihydroxyflavone 5,6,7-Trihydroxyflavone 1 2 1 Zinc Oxide 5 2 UV-Pearl,OMC 30 15 15 15 15 15 15 15 15 15 Polyglyceryl 3-Dimerate 3 3 3 3 3 3 33 3 3 Cera Alba 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 HydrogenatedCastor 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Oil Paraffinium Liquidum7 7 7 7 7 7 7 7 7 7 Caprylic/Capric 7 7 7 7 7 7 7 7 7 7 TriglycerideHexyl Laurate 4 4 4 4 4 4 4 4 4 4 PVP/Eicosene 2 2 2 2 2 2 2 2 2 2Copolymer Propylene Glycol 4 4 4 4 4 4 4 4 4 4 Magnesium Sulfate 0.6 0.60.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 Tocopherol 0.5 0.5 0.5 0.5 0.5 0.5 0.50.5 0.5 0.5 Tocopheryl Acetate 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5Cyclomethicone 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Propylparaben0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Methylparaben 0.150.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 Water to 100 to 100 to 100to 100 to 100 to 100 to 100 to 100 to 100 to 100 1-11 1-12 1-13 1-141-15 1-16 1-17 1-18 Titanium Dioxide 3 2 3 2 5 Benzylidene malonate 10.5 polysiloxane Methylene Bis- 1 1 0.5 BenztriazolylTetramethylbutylphenol 5,6,7-Trihydroxyflavone 5 3 2 5 1 3 7 2Polyglyceryl 3-Dimerate 3 3 3 3 Cera Alba 0.3 0.3 0.3 0.3 2 2 2 2Hydrogenated Castor 0.2 0.2 0.2 0.2 Oil Paraffinium Liquidum 7 7 7 7Caprylic/Capric 7 7 7 7 Triglyceride Hexyl Laurate 4 4 4 4 PVP/Eicosene2 2 2 2 Copolymer Propylene Glycol 4 4 4 4 Magnesium Sulfate 0.6 0.6 0.60.6 Tocopherol 0.5 0.5 0.5 0.5 Tocopheryl Acetate 0.5 0.5 0.5 0.5 1 1 11 Cyclomethicone 0.5 0.5 0.5 0.5 Propylparaben 0.05 0.05 0.05 0.05 0.050.05 0.05 0.05 Methylparaben 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15Dicocoyl Pentaerythrityl 6 6 6 6 Citrate (and) Sorbitan Sesquioleate(and) Cera Alba (and) Aluminum Stearate PEG-7 Hydrogenated 1 1 1 1Castor Oil Zinc Stearate 2 2 2 2 Oleyl Erucate 6 6 6 6 Decyl Oleate 6 66 6 Dimethicone 5 5 5 5 Tromethamine 1 1 1 1 Glycerin 5 5 5 5 Allantoin0.2 0.2 0.2 0.2 Water to 100 to 100 to 100 to 100 to 100 to 100 to 100to 100 1-19 1-20 1-21 1-22 1-23 1-24 1-25 1-26 1-27 1-28 1-29TitaniumDdioxide 2 5 3 3 Benzylidene Malonate 1 1 1 PolysiloxaneMethylene Bis- 1 2 1 1 Benztriazolyl Tetramethylbutylphenol Zinc oxide 52 6,3′,4′- 5 5 5 5 7 5 5 5 5 5 8 Trihydroxyflavone UV-Pearl, OCR 10 5UV-Pearl, 10 EthylhexylDimethyl- PABA UV-Pearl, Homosalate 10 UV-Pearl,Ethylhexyl 10 salicylate UV-Pearl, OMC, BP-3 10 UV-Pearl, OCR, BP-3 10UV-Pearl, Ethylhexyl 10 Dimethyl PABA, BP-3 UV-Pearl, Homosalate, 10BP-3 UV-Pearl, Ethylhexyl 10 salicylate, BP-3 BMDBM 2 UV-Pearl OMC, 254-Methylbenzylidene Camphor Polyglyceryl 3-Dimerate 3 3 3 3 3 3 3 3 3 33 Cera Alba 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 HydrogenatedCastor 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Oil ParaffiniumLiquidum 7 7 7 7 7 7 7 7 7 7 7 Caprylic/Capric 7 7 7 7 7 7 7 7 7 7 7Triglyceride Hexyl Laurate 4 4 4 4 4 4 4 4 4 4 4 PVP/Eicosene 2 2 2 2 22 2 2 2 2 2 Copolymer Propylene Glycol 4 4 4 4 4 4 4 4 4 4 4 MagnesiumSulfate 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 Tocopherol 0.5 0.50.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Tocopheryl Acetate 0.5 0.5 0.5 0.50.5 0.5 0.5 0.5 0.5 0.5 0.5 Cyclomethicone 0.5 0.5 0.5 0.5 0.5 0.5 0.50.5 0.5 0.5 0.5 Propylparaben 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.050.05 0.05 0.05 Methylparaben 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.150.15 0.15 0.15 Water to 100

[0242] TABLE 2 O/W emulsions, data in % by weight 2-1 2-2 2-3 2-4 2-52-6 2-7 2-8 2-9 2-10 Titanium Dioxide 2 5 3 Methylene Bis- 1 2 1Benztriazolyl Tetramethylbutylphenol 7,8,3′,4′- 1 2 1 1Tetrahydroxyflavone 4′-Methoxy-6- 1 3 2 5 5 2 hydroxyflavone 6,3′,4′- 55 5 5 5 5 5 5 5 5 Trihydroxyflavone 5,6,7-Trihydroxyflavone 1 5 4 6 7 21 4-Methylbenzylidene 2 3 4 3 2 Camphor BMDBM 1 3 3 3 3 3 3 StearylAlcohol (and) 3 3 3 3 3 3 3 3 3 3 Steareth-7 (and) Steareth-10 GlycerylStearate (and) 3 3 3 3 3 3 3 3 3 3 Ceteth-20 Glyceryl Stearate 3 3 3 3 33 3 3 3 3 Microwax 1 1 1 1 1 1 1 1 1 1 Cetearyl Octanoate 11.5 11.5 11.511.5 11.5 11.5 11.5 11.5 11.5 11.5 Caprylic/Capric 6 6 6 6 6 6 6 6 6 6Triglyceride Oleyl Oleate 6 6 6 6 6 6 6 6 6 6 Propylene Glycol 4 4 4 4 44 4 4 4 4 Glyceryl Stearate SE Stearic Acid Persea GratissimaPropylparaben 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05Methylparaben 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15Tromethamine 1.8 Glycerin Water to 100 to 100 to 100 to 100 to 100 to100 to 100 to 100 to 100 to 100 2-11 2-12 2-13 2-14 2-15 2-16 2-17 2-18Titanium Dioxide 3 2 2 5 Benzylidene Malonate Polysiloxane 1 0.5Methylene Bis-Benztriazolyl 1 1 0.5 Tetramethylbutylphenol4′-Methoxy-7-β-glucosidylflavone 1 2 7,8,3′,4′-Tetrahydroxyflavone 1 3 25 5 5,6,7-Trihydroxyflavone 5 5 5 5 5 5 5 5 6,3′,4′-Trihydroxyflavone 15 4 6 7 Zinc Oxide 2 UV-Pearl, OMC 15 15 15 30 30 30 15 154-Methylbenzyliden Camphor 3 BMDBM 1 Phenylbenzimidazole Sulfonic Acid 4Stearyl Alcohol (and) Steareth-7 (and) 3 3 3 3 Steareth-10 GlycerylStearate (and) Ceteth-20 3 3 3 3 Glyceryl Stearate 3 3 3 3 Microwax 1 11 1 Cetearyl Octanoate 11.5 11.5 11.5 11.5 Caprylic/Capric Triglyceride6 6 6 6 14 14 14 14 Oleyl Oleate 6 6 6 6 Propylene Glycol 4 4 4 4Glyceryl Stearate SE 6 6 6 6 Stearic Acid 2 2 2 2 Persea Gratissima 8 88 8 Propylparaben 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Methylparaben0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 Tromethamine 1.8 Glycerin 3 3 33 Water to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100 2-192-20 2-21 2-22 2-23 2-24 2-25 2-26 2-27 2-28 Titanium Dioxide 3 3 2Benzylidene Malonate 1 2 1 1 1 0.5 Polysiloxane 7,8,3′,4′- 1 2 1 1Tetrahydroxyflavone 5,6,7- 1 3 2 5 5 2 Trihydroxyflavone 6,3′,4′- 5 5 55 5 5 5 5 5 5 Trihydroxyflavone 4′,7-Dihydroxyflavone 1 5 4 6 7 2 1Methylene Bis- 1 2 1 1 1 0.5 Benztriazolyl Tetramethylbutylphenol ZincOxide 5 2 2 UV-Pearl, OMC 15 15 15 15 15 15 15 15 15 15 Caprylic/Capric14 14 14 14 14 14 14 14 14 14 Triglyceride Oleyl Oleate Propylene GlycolGlyceryl Stearate SE 6 6 6 6 6 6 6 6 6 6 Stearic Acid 2 2 2 2 2 2 2 2 22 Persea Gratissima 8 8 8 8 8 8 8 8 8 8 Propylparaben 0.05 0.05 0.050.05 0.05 0.05 0.05 0.05 0.05 0.05 Methylparaben 0.15 0.15 0.15 0.150.15 0.15 0.15 0.15 0.15 0.15 Glyceryl Stearate, Ceteareth-20,Ceteareth-10, Cetearyl Alcohol, Cetyl Palmitate Ceteareth-30 DicaprylylEther Hexyldecanol, Hexyldecyl Laurate Cocoglycerides TromethamineGlycerin 3 3 3 3 3 3 3 3 3 3 Water to 100 to 100 to 100 to 100 to 100 to100 to 100 to 100 to 100 to 100

[0243] TABLE 3 Gels, data in % by weight 3-1 3-2 3-3 3-4 3-5 3-6 3-7 3-83-9 3-10 a = aqueous gel Titanium Dioxide 2 5 3 5,6,7- 1 2 1 1Trihydroxyflavone 7,8,3′,4′- 1 3 2 5 5 2 Tetrahydroxyflavone 6,3′,4′- 55 5 5 5 5 5 5 5 5 Trihydroxyflavone 4′,7- 1 5 4 6 7 2 1 DihydroxyflavoneBenzylidene Malonate 1 1 2 1 1 Polysiloxane Methylene Bis- 1 1 2 1Benztriazolyl Tetramethylbutylphenol Zinc Oxide 2 5 2 UV-Pearl,Ethylhexyl 30 15 15 15 15 15 15 15 15 15 Methoxycinnamate4-Methylbenzylidene 2 Camphor Butylmethoxydibenzoylmethane 1Phenylbenzimidazole 4 Sulfonic Acid Prunus Dulcis 5 5 5 5 5 5 5 5 5 5Tocopheryl Acetate 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5Caprylic/Capric 3 3 3 3 3 3 3 3 3 3 Triglyceride Octyldodecanol 2 2 2 22 2 2 2 2 2 Decyl Oleate 2 2 2 2 2 2 2 2 2 2 PEG-8 (and) 0.05 0.05 0.050.05 0.05 0.05 0.05 0.05 0.05 0.05 Tocopherol (and) Ascorbyl Palmitate(and) Ascorbic Acid (and) Citric Acid Sorbitol 4 4 4 4 4 4 4 4 4 4Polyacrylamide (and) 3 3 3 3 3 3 3 3 3 3 C13-14 Isoparaffin (and)Laureth-7 Propylparaben 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.050.05 Methylparaben 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15Tromethamine 1.8 Water to 100 to 100 to 100 to 100 to 100 to 100 to 100to 100 to 100 to 100 3-11 3-12 3-13 3-14 3-15 3-16 3-17 3-18 a = aqueousgel a a a a a Titanium Dioxide 3 2 Benzylidene Malonate Polysiloxane 10.5 1 2 Methylene Bis-Benztriazolyl 1 1 0.5 1 2 1 Tetramethylbutylphenol7,8,3′,4′-Tetrahydroxyflavone 1 2 4′-Methoxy-6-hydroxyflavone 1 3 2 5 55,6,7-Trihydroxyflavone 5 5 5 5 5 5 5 5 6,3′,4′-Trihydroxyflavone 1 5 46 7 Zinc Oxide 2 UV-Pearl, Ethylhexyl Methoxycinnamate 15 15 15 15 15 1515 15 Prunus Dulcis 5 5 5 Tocopheryl Acetate 0.5 0.5 0.5 Caprylic/CapricTriglyceride 3 3 3 Octyldodecanol 2 2 2 Decyl Oleate 2 2 2 PEG-8 (and)Tocopherol (and) Ascorbyl 0.05 0.05 0.05 Palmitate (and) Ascorbic Acid(and) Citric Acid Sorbitol 4 4 4 5 5 5 5 5 Polyacrylamide (and) C13-14 33 3 Isoparaffin (and) Laureth-7 Carbomer 1.5 1.5 1.5 1.5 1.5Propylparaben 0.05 0.05 0.05 Methylparaben 0.15 0.15 0.15 0.15 0.15 0.150.15 0.15 Allantoin 0.2 0.2 0.2 0.2 0.2 Tromethamine 2.4 2.4 2.4 2.4 2.4Water to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100 3-19 3-203-21 3-22 3-23 3-24 3-25 3-26 3-27 3-28 7,8,3′,4′- 1 2 1 1Tetrahydroxyflavone 5,6,7- 1 3 2 5 5 2 Trihydroxyflavone 6,3′,4′- 5 5 55 5 5 5 5 5 5 Trihydroxyflavone 4′,7-Dihydroxyflavone 1 5 4 6 7 2 1UV-Pearl, OMC 30 30 15 15 15 11 12 15 15 15 Phenylbenzimidazole 4 4Sulfonic Acid Sorbitol 5 5 5 5 5 5 5 5 5 5 Carbomer 1.5 1.5 1.5 1.5 1.51.5 1.5 1.5 1.5 1.5 Propylparaben Methylparaben 0.15 0.15 0.15 0.15 0.150.15 0.15 0.15 0.15 0.15 Allantoin 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.20.2 Tromethamine 2.4 4.2 4.2 2.4 2.4 2.4 2.4 2.4 2.4 2.4 Water to 100 to100 to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100 3-29 3-303-31 3-32 3-33 3-34 3-35 3-36 4′-Methoxy-7-β-glucosidylflavone 1 27,8,3′,4′-Tetrahydroxyflavone 1 3 2 5 5 6,3′,4′-Trihydroxyflavone 5 5 55 5 5 5 5 5,6,7-Trihydroxyflavone 1 5 4 6 7 UV-Pearl, OMC 15 10 10 10 1015 10 UV-Pearl, OCR 10 UV-Pearl, OMC, Methylene Bis- 7 6 BenzotriazolylTetramethylbutylphenol UV-Pearl, Ethylhexyl salicylate, 10 BMDBMDisodium Phenyl Dibenzimidazole 3 3 3 Tetrasulfonate PhenylbenzimidazoleSulfonic Acid 2 2 3 3 Prunus Dulcis 5 5 5 Tocopheryl Acetate 0.5 0.5 0.5Caprylic/Capric Triglyceride 3 3 3 Octyldodecanol 2 2 2 Decyl Oleate 2 22 PEG-8 (and) Tocopherol (and) Ascorbyl 0.05 0.05 0.05 Palmitate (and)Ascorbic Acid (and) Citric Acid Sorbitol 4 4 4 5 5 5 5 5 Polyacrylamide(and) C13-14 3 3 3 Isoparaffin (and) Laureth-7 Carbomer 1.5 1.5 1.5 1.51.5 Propylparaben 0.05 0.05 0.05 Methylparaben 0.15 0.15 0.15 0.15 0.150.15 0.15 0.15 Allantoin 0.2 0.2 0.2 0.2 0.2 Tromethamine 2.4 2.4 2.42.4 2.4 Water to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100

[0244] From the foregoing description, one skilled in the art can easilyascertain the essential characteristics of this invention and, withoutdeparting from the spirit and scope thereof, can make various changesand modifications of the invention to adapt it to various usages andconditions.

1. A composition having antioxidant properties comprising at least onecompound of the formula I

where R¹ to R¹⁰ may be identical or different and are selected from HOR¹¹ straight-chain or branched C₁- to C₂₀-alkyl groups, straight-chainor branched C₃- to C₂₀-alkenyl groups, straight-chain or branched C₁- toC₂₀-hydroxyalkyl groups, where the hydroxyl group(s) are bonded to aprimary or secondary carbon atom of the chain and furthermore the alkylchain is optionally interrupted by oxygen, and/or C₃- to C₁₀-cycloalkylgroups and/or C₃- to C₁₂-cycloalkenyl groups, where the rings are eachoptionally bridged by —(CH₂)_(n)— groups, where n=1 to 3, where all OR¹¹are, independently of one another, OH straight-chain or branched C₁- toC₂₀-alkoxy groups, straight-chain or branched C₃- to C₂₀-alkenyloxygroups, straight-chain or branched C₁- to C₂₀-hydroxyalkoxy groups,where the hydroxyl group(s) are bonded to a primary or secondary carbonatom of the chain and furthermore the alkyl chain is optionallyinterrupted by oxygen, and/or C₃- to C₁₀-cycloalkoxy groups and/or C₃-to C₁₂-cycloalkenyloxy groups, where the rings are each optionallybridged by —(CH₂)_(n)— groups, where n=1 to 3, and/or mono- and/oroligoglycosyl radicals, with the proviso that: at least 3 radicals fromR¹ to R⁷ are OH and that at least 2 pairs of adjacent —OH groups arepresent in the molecule, or R², R⁵ and R⁶ are OH and the radicals R¹,R³, R⁴ and R⁷⁻¹⁰ are H.
 2. The composition of claim 1, comprising atleast one compound of the formula I wherein at least two adjacentradicals of the radicals R¹ to R⁴ are OH and at least two adjacentradicals of the radicals R⁵ to R⁷ are OH.
 3. The composition of claim 1,comprising at least one compound of the formula I wherein at least threeadjacent radicals of the radicals R¹ to R⁴ are OH.
 4. The composition ofclaim 1, comprising at least one compound of the formula I wherein theradicals R¹ to R³ are OH.
 5. The composition of claim 1, comprising oneor more compounds of the formula I in an amount of from 0.01 to 20% byweight.
 6. The composition of claim 1, comprising one or more compoundsof the formula I in an amount of from 0.1 to 10% by weight.
 7. Acomposition of claim 1, for the protection of body cells againstoxidative stress, which further comprises one or more other antioxidantsand/or vitamins.
 8. The composition of claim 7, wherein at least oneother anti-oxidant or vitamin is vitamin A palmitate, vitamin C or aderivative thereof, DL-α-tocopherol, tocopherol E acetate, nicotinicacid, pantothenic acid or biotin.
 9. A composition of claim 1, whichfurther comprises one or more UV filters.
 10. The composition of claim9, wherein at least one UV filter is selected from the group consistingof 3-(4′-methylbenzylidene)-dl-camphor,1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione,4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octylmethoxycinnamate, 3,3,5-trimethylcyclohexyl salicylate, 2-ethylhexyl4-(dimethylamino)benzoate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate,2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium andtriethanolamine salts.
 11. The composition of claim 1, which compositionis a food or a food supplement and comprises an excipient which issuitable for a food or a food supplement.
 12. A process for preparing acomposition of claim 1, which comprises mixing a compound of the formulaI with an excipient which is suitable cosmetically or dermatologicallyor for food.
 13. A process according to claim 12, wherein the compoundof the formula I is prepared by reacting a 2-hydroxyacetophenonecompound with a lithium compound and subsequently a keto compound.
 14. Amethod for achieving an anti-oxidant effect on a patient which comprisesadministering to the patient a composition of claim
 1. 15. The method ofclaim 14, wherein the composition is applied to the skin.
 16. The methodof claim 14, wherein the composition further comprises at least one UVfilter compound.
 17. The method of claim 16, wherein at least one UVfilter compound is a dibenzoylmethane compound.
 18. A composition ofclaim 1, which is in the form of an emulsion.